From the consideration of the requirement of the state traditional Chinese medicine ( TCM ) clinical research facility (Hubei), this article focused on the establishment of the study and exploitation of TCM plat-form which serves exploitation of the hospital pharmaceuticals and new pharmaceuticals of key diseases such as liver disease . After 5 years of construction , the platform with innovative ability was initially formed; some characteristic pharmaceuticals were exploited, which promoted the clinical service ability of key disease, brought good economic and social influence . This article made a preliminary discussion on the construction achieve-ments , experiences and expectations of this platform .

Objective To evaluate the diagnostic values of microRNAs (miRNAs) as plasma biomarkers for early diagnosis of non-small cell lung cancer (NSCLC). Methods The levels of 10 miRNAs in plasma of 59 patients with early stage (stage Ⅰ-ⅢA) NSCLC (lung cancer group) and 59 benign lesions (control group) were detected by real-time quantitative polymerase chain reaction (RT-PCR). The levels of serum cytokeratins antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and other tumor markers were detected by electrochemiluminescence immunoassay (ECLIA), chemiluminescence immunoassay (CLIA) and immunoradiometric assay (IRMA). The early diagnostic value of miRNAs and other markers were evaluated by receiver-operating-characteristic (ROC) curve analysis. The sensitivity, specificity and area under the curve were calculated for the cut-off value. Results Plasma CYFRA21-1, miR-486 and miR-210 levels were significantly different in lung cancer group and control group (CYFRA21-1: 8.896±3.681 vs. 5.892±2.028, P= 0.020; miR-486:2.778±0.778 vs. 1.746±0.892, P< 0.001;miR-210: 4.836 ±1.374 vs. 2.829 ±1.503, P< 0.001). Area under ROC curve of CYFRA 21-1, miR-486 and miR-210 was 0.624 (sensitivity: 0.576, specificity: 0.797), 0.848 (sensitivity: 0.831, specificity: 0.780) and 0.751 (sensitivity: 0.746, specificity: 0.746), respectively. MiR-486, miR-210 combined with CYFRA21-1 had the highest diagnostic efficiency, and the area under the curve was 0.924 (sensitivity: 0.847, specificity:0.811), miR-486 combined with miR-210 had the highest diagnostic efficiency, and the area under the curve was 0.892 (sensitivity: 0.831, specificity: 0.780). Conclusions MiR-486 and miR-210 could be potential biomarkers for diagnosis of NSCLC. Plasma miRNAs combined with tumor markers can improve the diagnostic efficacy of early stage NSCLC.

To establish the quality standard for Zhike Xiaoyan Zhitong lotion. Methods: Phellodendri chinensis Cor-tex, Angelicae sinensis Radix and Astragali Radix in the preparation were identified by TLC. The content of berberine hydrochloride, the effective component in Phellodendri chinensis Cortex, was determined by HPLC with the chromatographic conditions as follows: an Agilent 5 TC-C18 column (250 mm × 4. 6 mm, 5 μm) was used, the mobile phase was acetonitrile-0. 05 mol·L-1 potassium dihydro-gen phosphate (30∶70) with the flow rate of 1. 0 ml·min-1 , the detection wavelength was 265 nm, and the column temperature was at 30 ℃. Results:The spots of Phellodendri chinensis Cortex, Angelicae sinensis Radix and Astragali Radix in Zhike Xiaoyan Zhitong lotion on TLC were clear with strong specificity and without any interference from the negative controls. There was a good linear rela-tionship for berberine hydrochloride within the range of 0. 029-3. 628 μg(r=0. 999 9), and the average recovery was 97. 83% (RSD=2. 05%, n=6). Conclusion:The qualitative and quantitative methods are accurate, reliable and repeatable, which can effectively control the inherent quality of Zhike Xiaoyan Zhitong lotion.

Objective:To analyze the protein expression changes in the retina of non-arteritic anterior ischemic optic neuropathy (NAION) in rats.Methods:The rat NAION (rNAION) model was established by Rose Bengal and laser. Twenty Sprague-Dawley rats were randomly divided into 4 groups, the normal control group, the laser control group, the RB injection control group, and the rNAION model group, with 5 rats in each group. The right eye was used as the experimental eye. The retina was dissected at the third day after modeling. Enzyme digestion method was used for sample preparation and data collection was performed in a non-dependent collection mode. The data were quantitatively analyzed by SWATH quantitative mass spectrometry, searching for differential proteins and performing function and pathway analysis.Results:Compared with the other three control groups, a total of 184 differential proteins were detected in the rNAION group (expression fold greater than 1.5 times and P<0.05), including 99 up-regulated proteins and 85 down-regulated proteins. The expressions of glial fibrillary acidic protein, guanine nucleotide binding protein 4, laminin 1, 14-3-3γ protein YWHAG were increased. Whereas the expressions of Leucine-rich glioma-inactivated protein 1, secretory carrier-associated membrane protein 5, and Clathrin coat assembly protein AP180 were decreased. The differential proteins are mainly involved in biological processes such as nerve growth, energy metabolism, vesicle-mediated transport, the regulation of synaptic plasticity, apoptosis and inflammation. Pathway enrichment analysis showed that PI3K-Akt signaling pathway and complement and thrombin reaction pathway was related to the disease. Conclusion:The protein expressions of energy metabolism, nerve growth, synaptic vesicle transport and PI3K-Akt signaling pathway can regulate the neuronal regeneration and apoptosis in NAION.

Hepatitis B virus (HBV) infection is a major global public health issue. Clinical cure (also known as functional cure) of chronic hepatitis B (CHB) is the ideal therapeutic goal recommended by the latest guidelines for the prevention and treatment of CHB in China and globally. Optimized treatment regimens with direct-acting antiviral agents ［e.g., nucleos(t)ide analogues］ or immunomodulators (e.g., pegylated interferon-α) sequentially or in combination tend to have low cure rates. Rapid development has been achieved in the research and development of drugs for the treatment of CHB. This article reviews the clinical study of new antiviral drugs for CHB, including the selection of subjects, study design, dosage, dose escalation, adverse events, and efficacy evaluation. It is necessary to introduce the knowledge of quantitative pharmacology to analyze the association of drug exposure in body with efficacy and adverse reactions, and exploratory indicators should be incorporated for comprehensive analysis. This review provides related experience and new ideas for the clinical research and development of new anti-HBV drugs.

Objective:To validate the role of color Doppler ultrasound in an animal model to detect early heterotopic ossification (HO) after brain-traumatic/burn/tenotomy.Methods:Forty-four rats were randomly divided into two groups. Rats in experimental group ( n=22) were operated to build brain-traumatic/burn/tenotomy model and others in control group ( n=22) underwent only skin incision injury. Color Doppler ultrasound, X-ray film examination at 2, 3, 4, 6, 8 and 10 weeks post-injury were performed to follow up the progression of HO in both groups respectively. Histology was used to confirm bone formation. Results:In the experimental group, disorder structure with a hypoechoiccore in treated Achilles tendon was visualized using color Doppler ultrasound in the 2nd week. Additional tiny hyperechoic foci were observed in the 3rd week, which increased in the fourth week and fused into a mineralized island in the sixth week. No obvious abnormality was found in control group at the aforementioned time point. X-ray could detect heterotopic bone tissue in the sixth week in the experimental group but not in the control group. X-ray and HE stainning had confirmed bone formation in the tenth week in the experimental group.Conclusions:Color Doppler ultrasound can detect early HO and continuously follow up the progression of HO.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to mortality and prognosis, and the 5-year survival rate for all patients diagnosed with ESCC remains poor. A better understanding of the biological mechanisms of ESCC tumorigenesis and progression is of great importance to improve treatment of this disease. In this study, we demonstrated that the glutathione metabolism pathway is highly enriched in ESCC cells compared with normal esophageal epithelial cells in an in vivo mouse model. In addition, treatment with L-buthionine-sulfoximine (BSO) to deplete glutathione decreased the ESCC tumor burden in mice, thus demonstrating the critical role of glutathione metabolism in ESCC progression. BSO treatment also led to decreased cell proliferation and activation of cell apoptosis in ESCC. Finally, BSO treatment blocked NF-κB pathway activation in ESCC. Our study reveals a new pathway that regulates ESCC progression and suggests that inhibition of glutathione metabolism may be a potential strategy for ESCC treatment.
Animals ; Apoptosis ; Carcinogenesis ; Carcinoma, Squamous Cell ; Cell Proliferation ; Epithelial Cells ; Esophageal Neoplasms* ; Glutathione* ; Humans ; Metabolism* ; Mice ; Mortality ; Prognosis ; Survival Rate ; Tumor Burden

Objective To investigate the prevalence of urine abnormalities for school children in Chengdu city and to evaluate the significance of urinary screening.Methods During January to December 2013,morning urine of 6 615 students were collected and screened by urine reagent paper.Two weeks later,the repeated screening was conducted in the children whose urine samples were positive for the first screening.Urine samples with positive testing results for twice were submitted to urine routine tests at local hospital,and the children with the urine positive results were defined as urine abnormalities.The children with urine abnormalities were transferred to a tertiary hospital and given treatment and follow-up.Results There were 6 615 cases receiving urine screening,including 2 624 cases (39.67 ％) of the grade I,and 3 991 cases(60.33％) at junior middle school.During the first screening,323 cases (4.83％) children had urinary occult blood positive,43 cases (0.65％) had urinary protein,20 cases (0.30％) had occult blood positive and proteinuria,and 103 cases (1.56％) had white cells in urine.During the second urine screening,62 cases (0.94％) had occult blood positive,6 cases (0.09％) had urinary protein,2 cases (0.03％) had proteinuria and occult blood positive,46 cases (0.70％) had white cells in urine.The incidence of urine abnormalities with occult blood positive,proteinuria,occult blood positive and proteinuria,and white cells in urine of children at junior middle school [1.38％ (55/3 991 cases),0.13％ (5/3 991 cases),0.05％ (2/3 991 cases),0.70％ (28/3 991 cases)] were significantly higher than those of children at primary school [0.27％ (7/2 624 cases),0.04％ (1/2 624 cases),0 (0/ 2 624 cases),0.69％ (18/2 624 cases)],and all the differences were statisticallysignificant (x2 =64.16,168.53,178.09,98.16,all P ＜ 0.05).In children transferred to a tertiary hospital for treatment,there were 4 cases with IgA nephropathy,1 case with minor glomerular abnormalities,and 12 cases with urinary tract infection.Conclusion Urinary screening is an effective way to find out kidney disease and urinary tract infection in children.Follow-ups should be strengthened.

Objective To explore the correlation between serum glycosylated hemoglobin(HbA1c),lym-phocyte activation gene-3(LAG-3)and thyroid nodules in patients with type 2 diabetes mellitus(T2DM).Methods A total of 120 T2DM patients with thyroid nodules admitted to the Third Hospital of Hebei Medi-cal University from July 2021 to July 2022 were included as the study group,and 100 simple T2DM patients(without thyroid nodules)were included as the control group during the same period.According to the patho-logical examination results of thyroid nodules,the study group was grouped into a benign nodule group(85 ca-ses)and a malignant nodule group(35 cases).Enzyme linked immunosorbent assay was applied to detect the serum LAG-3 level of all study subjects.Fully automated glycated hemoglobin analyzer was applied to detect HbA1c level in all study subjects.Spearman method was applied to analyze the correlation between serum HbA1c,LAG-3,and thyroid imaging report and data system(TI-RADS)scores in patients with T2DM and thyroid nodules.Multivariate Logistic regression was applied to analyze the influencing factors of T2DM with thyroid nodules.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of HbA1c and LAG-3 levels in T2DM with thyroid nodules.Results Compared with the control group,the level of HbA1c in the study group was obviously higher(P<0.05),while the level of LAG-3 was obviously lower(P<0.05).Compared with the benign nodule group,the serum LAG-3 level in the malignant nodule group was obviously lower(P<0.05),while the level of LAG-3 was obviously lower(P<0.05).Spearman analysis showed a positive correlation between HbA1c level and TI-RADS score in T2DM patients with thyroid nod-ules(r=0.378,P<0.001),while the serum LAG-3 level was negatively correlated with TI-RADS score(r=-0.472,P<0.001).The results of multivariate Logistic regression analysis showed that HbA1c was a risk factor for the occurrence of thyroid nodules in T2DM patients(P<0.05),and LAG-3 was a protective factor for the occurrence of thyroid nodules in T2DM patients(P<0.05).The combination of HbA1c and LAG-3 in the diagnosis of T2DM with thyroid nodules was superior to their individual diagnosis(Zcombination-HbA1c=2.542,P=0.011;Zcombination-LAG-3=3.098,P=0.002).Conclusion Patients with T2DM combined with thyroid nodules have obviously lower serum LAG-3 level and higher HbA1c level,and the two are related to the malignancy of thyroid nodules.

Objective:To quantitatively analyze the protein expression changes of the optic nerve in an SD rat model of non-arteritic anterior ischemic optic neuropathy (NAION), and to make bioinformatics analysis of the differential proteins.Methods:Ten 8-week-old SPF male SD rats with a body mass of 200-250 g were selected.The NAION model was established using the method of rose bengal and laser photodynamics.Four from the 8 rats with successful model were selected as the NAION model group.Another 4 body weight- and age-matched healthy SD rats without eye diseases were taken as the normal control group.The optic nerve was dissected on the 7th day after modeling.The samples were prepared by the enzyme digestion method, and the proteins were identified and quantitatively detected by isobaric tag for relative and absolute quantification labeling combined with liquid chromatography-tandem mass spectrometry.The proteins with expression fold greater than 1.5 times and significant differences between the two groups ( P<0.05) were defined as differentially expressed proteins and analyzed by bioinformatics.The use and care of animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by the State Science and Technology Commission of China.The study protocol was approved by an Animal Ethical and Welfare Committee of Tianjin Medical University Eye Hospital (No.TJYY2021041029). Results:Three days after modeling, the optic disc of rats was swollen and fluorescein leakage in the optic disc was detected in fluorescein fundus angiography images in the NAION model group, which indicated the model was established successfully.A total of 1 291 quantifiable proteins including 80 differentially expressed proteins were identified.Compared with the normal control group, there were 5 up-regulated proteins and 75 down-regulated proteins.The expression levels of collagen alpha-1(V) chain (Col5A1), cAMP-dependent protein kinase catalytic subunit beta (Prkacb) and disks large homolog 1(Dlg1) were increased, and the expression levels of neurofilament medium polypeptide (Nefm), microtubule-associated protein 1B (Map1b), Ras-related protein Ral-A (Rala), serine/threonine-protein kinase N2 (Pkn2) and platelet-activating factor acetylhydrolase IB subunit beta (Pafah1b1) were decreased.Differentially expressed proteins were mainly involved in the biological processes, including regulation of the cytoskeleton, cellular response to hypoxia, axon production and extension, regulation of synapse, regulation of neuron apoptosis and axo-dendritic transport, etc.KEGG pathway enrichment analysis showed that differentially expressed proteins were mainly involved in metabolic pathways, synaptic vesicle circulation and platelet activation.Conclusions:The expression of proteins related to signal pathways such as nerve growth, energy metabolism, axo-dendritic transport and apoptosis is involved in the apoptosis of neurons in NAION.