Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Diseases ; drug therapy

Objective: To examine the effect of SiO2 exposure on the airway surface microenvironment and NIMA-related kinase 7 (NEK7)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in rats. Methods: Twenty-four specific pathogen-free male rats of the SD strain were randomly divided into the control group and the model group, of 12 rats in each group. Rats in the model group were given SiO2 suspensions through disposable tracheal intubation perfusion to model silicosis in rats, while rats in the control group was perfused with the same amount of physiological saline. The pH value and glucose level were measured in the rat bronchoalveolar lavage fluid (BALF) 14 and 28 days after modeling. Lung tissues were stained with HE and Masson and the distribution of inflammatory cells and the deposition of pulmonary interstitial collagens were observed in lung tissues under a light microscope. The expression of transforming growth factor β1 (TGF-β1), collagen type Ⅰ(ColⅠ), collagen type Ⅲ (Col Ⅲ), interleukin-1β (IL-1β), NLRP3, N-terminal domain of Gasdermin D (GSDMD-NT), caspase-1, and NEK7 was quantified in lung specimens using immunohistochemistry. Results: Lower pH values were measured in rat BALF in the model group than in the control group 14 [(6.38±0.05) vs. (6.68±0.08), P<0.05] and 28 days after modeling [(6.63±0.14) vs. (6.86±0.05), P<0.05], while higher glucose levels were seen in the model group than in the control group 14 [(0.39±0.06) vs. (0.31±0.04) mg/dL, P<0.05] and 28 days after modeling [(0.39±0.08) vs. (0.31±0.06) mg/dL, P<0.05]. HE and Masson staining showed mild to moderate alveolitis and pulmonary fibrosis in rats 14 days post-exposure to SiO2, and showed moderate to severe alveolitis and pulmonary fibrosis 28 days post-exposure. Immunohistochemistry detected higher TGF-β1, ColⅠ, Col Ⅲ, IL-1β, NLRP3, GSDMD-NT, caspase-1 and NEK7 expression in rat lung tissues in the model group than in the control group (all P<0.05). Conclusions SiO2 exposure may cause changes in rat airway surface microenvironment, including BALF acidification and elevated glucose. Pyroptosis induced by activation of NEK7-associated NLRP3 inflammasome may be an important mechanism of pulmonary fibrosis caused by silicosis.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

Mean hemoglobin (Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders (Tibetans, Sherpas, and Ladakhis) was compared with lowlanders (Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness (CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.
Adaptation, Physiological ; Altitude ; Asian Continental Ancestry Group ; genetics ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Evolution, Molecular ; Hemoglobins ; genetics ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases ; genetics ; Tibet

OBJECTIVE: To explore the effects of Salvia miltiorrhiza on renal morphology and renal function of rats with streptozotocin diabetes. METHODS: Thirty male Wistar rats were randomly divided into three groups, which were normal control group, untreated group and Salvia miltiorrhiza-treated group. Diabetic nephropathy was induced in rats of the last two groups by intraperitoneal injection of streptozotocin after unilateral nephrectomy. Then the rats in the normal control and untreated groups were fed with normal saline while those in the Salvia miltiorrhiza-treated group were fed Salvia miltiorrhiza preparation for 8 weeks. The glomerular volume (VG), kidney-to-body weight ratio (KW/BW), urinary albumin excretion rate (UAER) and creatinine clearance (Ccr) were observed. The expression levels of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) were detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at the end of the experiment. RESULTS: UAER, Ccr, VG and KW/BW ratio were significantly higher in the untreated group than those in the normal control group (P<0.05). The expression levels of TGF-beta1, CTGF, PAI-1 and FN in the untreated group were also significantly higher as compared with those in the normal control group (P<0.05). UAER, Ccr, VG, KW/BW ratio and the levels of TGF-beta1, CTGF, PAI-1 and FN in the Salvia miltiorrhiza-treated group were obviously lower than those in the untreated group (P<0.05). CONCLUSION: Salvia miltiorrhiza can protect rats with streptozotocin diabetes from diabetic nephropathy by suppressing the over-expressions of TGF-beta1, CTGF, PAI-1 and FN in renal cortex.

Objective To construct the recombinant plasmid pYES6-S and express and purify spike protein of severe acute respiratory syndrome(SANS)coronavirus in Saccharomyces cerevisiae. Methods DNA fragments of SANS coronavirus were obtained by reverse transeription.Four over- lapped fragments of spike protein genes were amplified by polymerase chain reaction(PCR)and ligated into an integral spike protein gene by restriction enzyme digestion.The spike protein gene recombined with pYES6 and cloned into E.coll.The recombinant plasmid pYES6-S was induced and expressed in Saccharomyces cerevisiae(INVScl)by galactose.Results The recombinant plasmid pYES6-S was confirmed that inserted fragment was right in length,direction and base matching by restriction enzyme digestion and sequencing.The purified protein encoded by the whole spike protein gene was about Mr 110?10~3 identified by electrophoresis.Conclusion The whole spike protein gene of SARS coronavirus is cloned into E.coli and the protein is expressed in Saccharomyces cerevisiae successful ly.which can be helpful in SARS vaccine research.

Objectives To estimate the prevalence of the cardiovascular health (CVH) status in south Jiangsu adults. Methods A cross-sectional study was conducted, a total of 11 996 participants that took health examination in hospitals from March 2013 to August 2013 and live in south Jiangsu were selected. Results Totally 136 participants (1.1%) met all 7 ideal CVH metrics;while 27.6%participants met 5 to 7 ideal CVH metrics, women had higher proportion (47.2%) than men (16.9%). The percentage of participants who met 5 to 7 ideal CVH metrics, whether male or female, decreased with increasing age. Ideal total cholesterol (TC) was the most prevalent (72.0%), whereas ideal salt intake was the least (19.9%). The mean (± SD) number of ideal CVH metrics for urban participants was (3.61 ± 1.46), higher than the rural participants (3.45±1.49). Old age, male and residence in rural area were risk factors for ideal CVH metrics≥5. Conclusions The prevalence of ideal CVH was extremely low in South Jiangsu adults, and there were differences in the distribution of ideal CVH metrics across gender and age. To improve CVH, specific promotion and interventions at the population and individual levels should be developed and implemented actively.

Objective To compare early-stage clinical features and hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine function in first-episode and untreated major depressive disorders with suicide and without suicide. Methods Untreated patients who had a diagnosis as major depression according to ICD-10 were allocated to suicide with major depressive disorder group or non-suicide with major depressive disorder group according to whether the pa?tients had suicidal ideation or behaviours. Patients were assessed before treatment using the 17-item Hamilton Depres?sion Scale (HAMD-17), the Hamilton Anxiety Scale (HAMA), the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the suicide assessment scale. The cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in serum were measured using a chemiluminescence immunoassay. Results There was no significant difference in demographic data be?tween the two groups (P>0.05). In early-stage clinical features, there were significant differences in changes of sexual ac? tivity and feeling of despair (P<0.05). HAMD total scores were significantly higher in the suicide group (P<0.01), whereas HAMA total scores and Y-BOCS total scores were not significantly different between the two groups (P>0.05). There were no significant differences in CORT or ACTH levels between two groups (P>0.05). There were no significant correlation of suicidal scores with early-stage clinical features, symptom scales scores, CORT or ACTH levels (P>0.05). Conclusion De?creased sexual desire and feeling of despair are more severe in depressed patients with suicide than those without. There is no correlation of early-stage clinical features or HPA axis functions with suicide in patients with depression.

Objective:To investigate the clinic-cytology and histopathology of non-Hodgkin lymphoma (NHL) in breasts. Mothods:Twelve cases of NHL of the breast were studied by fine-needle aspiration biopsy (FNAC), histopathology and immunohistochemistry, and whose clinical data were analysed at the same time. Results:In 12 cases of NHL, 3 cases were T-cell NHL and 9 cases were B-cell NHL. Cytologically, the T-cell NHL cells were mostly arranging in diffuse patterns. The tumor cells were oval and pleomorphism. Some of them had distorted nucleus and thin nuclear envelope.The nucleus showed irregular course chromatin and visible nueleoic. Histopathologically, some of the tumor cells distributed around the blood vessels, and there was an obvious phenomenon of “blood-vessel-closing”. B-cell lymphoma cells were arranginy in diffuse pattern, and showed round and ellipse in shape with a clot and course granular chromatin and visible nueleoic and karyoknesis. Lymphoepithelia lesions were seen. Immunohistochemistry showed that CD3, CD43, and CD 45RO in T-cells NHL were positive.CD20, CD74 and CD79a in B-cells NHL were negative. CK, EMA, ER and PR in NHL were all negative. Conclusion:NHL of breast is extremely rare, and its definite diagnosis depends on various examination methods.

A reverse transcription polymerase chain reaction (RT-PCR) and single-strand conformation polymorphisms (SSCP) assay were applied to rapidly detect the molecular variability in CP and SP genes among seven isolates of Rice stripe virus in China. The PCR results showed that the CP gene of JD isolate and SP gene of PJ isolate could not be amplified. SSCP analysis showed that there were completely different electrophoretic pattern of CP gene among six isolates. To SP gene, SSCP results also discovered polymorphisms. There were five patterns among these isolates, and the pattern of YL and BS isolates were same.