Objective To observe the histopathologic injury of small intestine and intestinal permeability in chronic renal failure (CRF) rats. Methods Twenty male Sprague-Dawley rats were randomly assigned to CRF group (n=10) and control group (n=10). 5/6 nephrectomy was used to establish CRF rats, while sham operation for control. Blood biochemistry was regularly monitored until CRF model was successfully established. The model rats were fed with lactulose (L) and mannitol (M) through intragastric administration. Urine was collected after 6 hours, and the concentration of lactulose and mannitol in urine was measured using high pressure liquid chromatograph with refractive index detector (HPLC-RID), and the ratio of urinary excretion of L/M was calculated to evaluate intestinal permeability. Small intestinal mucosa were stained by hematoxylin-eosin (HE) and observed with light microscope (villus height, thickness of muscle layer and villus count), histological damage score was used to evaluate intestinal injury. Results The L/M ratio of CRF group was higher than that of control group (1.75±0.11 vs 1.20±0.06, P<0.01). The small intestinal mucosal villus height and thickness of muscle layer in CRF group were higher (P<0.01), and the number of villi was lower compared to control group (P<0.01). The score of histopathologic intestine damage of CRF group was higher than that of control group (1.00±0.71 vs 0, P<0.01). Conclusion The intestinal permeability of CRF rats is increased with varying degrees of intestinal damage.

c-Met is one member of the receptor tyrosine kinases (RTKs).It is closely related between the over-expression of c-Met and a wide variety of tumor occurrence, development, invasion, metastasis, prognosis and drug resistance.Therefore, c-Met is a potential target for oncotherapy, and researches on its inhibitors have become a hot spot in the field of tumor treatment.Aptamers targeting c-Met are gained from systematic evolution of ligands by exponential enrichment (SELEX).They can bind to c-Met with high specificity and affinity, resulting in the activation or inhibition of c-Met.We envision that anti-c-Met aptamers would be ideal new c-Met inhibitors after optimization, and could be developed into potential targeted drugs for cancers.

Objective The article was to observe the clinical efficacy of the application of terbinafine and mizolastine in com -bined treatment of chronic eczema ( CE) with dermatophytes infection , so as to define the etiology role of dermatophytes in allergic dis-eases. Methods All subjects were randomly divided into experiment group and control group .The experiment group was treated with the combination of terbinafine and mizolastine , while the control group took mizolastine orally alone .EASI grading , recovery rate and effective rate were evaluated at 2, 3 week after the treatment and EASI grading and recurrence rate were evaluated at 4 weeks after the treatment. Results 79 patients had finished the experiment .Significant difference was found in the effective rates between two groups at 3 weeks after treatment (P<0.05).At 4 weeks after the treatment, EASI value and recurrence rate in experiment group were obviously lower than those in control group (P<0.05). Conclusion Good therapeutic effect has been achieved through the ap-plication of terbinafine and mizolastine in combined treatment of CE with dermatophytes infection , which implies dermatophytes plays an important role in the etiology of CE .

OBJECTIVETo improve the oral bioavailability of patchoulic alcohol in rats by using self-microemulsifying drug delivery systems (SMEDDS).

METHODPatchoulic alcohol was separated and purified from patchoulic oil, and the SMEDDSs including patchoulic alcohol or patchoulic oil were optimized by pseudo-ternary phase diagrams via central composite design-response surface methodology. Pharmacokinetics of both SMEDDSs and patchoulic alcohol itself in rats were investigated.

RESULTThe patchoulic alcohol SMEDDS (Cremophor EL-Tween 80-PEG 400-isopropyl myristate-patchoulic alcohol, 2:2:0.8:1.95:0.65) was considered as the optimized formulation. The mean drop size of the system was 30. 1 nm after diluted 100 folds in water. The average self-microemulsifying time was 142 s. Patchoulic alcohol SMEDDS and patchoulic oil SMEDDS showed no signficant difference in Tmax compared with patchoulic alcohol with around 60 minutes, while the AUCs of both SMEDDSs (2001 745.6 +/- 329 663.6) and (1594 005.6 +/- 280 150.3) microg x min x L(-1) were significantly higher than that of patchoulic alcohol (1 163 153.3 +/- 232 324.3) microg x min x L(-1).

CONCLUSIONSMEDDS can effectively improve the oral bioavailability of patchoulic alcohol in rats.

Administration, Oral ; Animals ; Biological Availability ; Chemistry, Pharmaceutical ; Drug Delivery Systems ; methods ; Drug Stability ; Emulsifying Agents ; chemistry ; Ethanol ; chemistry ; Female ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Self Administration ; Sesquiterpenes ; chemistry ; Solubility

Objective:To describe the epidemiological characteristics of mental disorders in Ximeng Wa Au-tonomous County and explore psychosocial risk factors of mental disorders. Methods:Two thousand three hundred and eighty one residents aged 1 8 years and over were sampled using multistage sampling in Ximeng Wa Autono-mous County in 2013. All respondents were investigated by face-to-face interview. Mental disorders were screened out by using the General Health Questionnaire (GHQ)and diagnosed according to the International Classification of Diseases Checklist (ICD-10-Checklist)criteria. Results:Life time prevalence of any mental disorder was 19. 86%(419/2110). The lifetime prevalence rates of substance use disorder,anxiety disorder,insomnia,mood disorder, schizophrenia were 12. 99%(274/2110),6. 30%(133/2110),2. 94%(62/2110),2. 32%(49/2110)and 1. 00%(21/2110)respectively. Male (OR=0. 43),older age (35 -49 years,OR=1. 78;50 -64 years,OR=2. 59;≥65 years,OR=3. 5 1 ),unmarried and other marital status (OR=0. 3 1 ),non-Wa and non-Lahu ethnic groups (OR=0. 29)were associated with neurotic,stress-related and somatoform disorders. Male (OR=2. 41),older age (35 -49 years,OR=2. 29;50-64 years,OR=3. 20;≥65 years,OR=4. 58),non-farmer and non-self-employed occupation (OR=0. 41),and non-Wa and non-Lahu ethnic groups (OR=0. 32)were associated with psychoactive substance use disorder. Male (OR =0. 35 ) and order age (≥65 years,OR =3. 05 ) were associated with mood disorders. Conclusion:Lifetime prevalence of any mental disorder,substance use disorders and anxiety disorders are high in Ximeng Wa Autonomous County. Measures should be strengthened against prevalence of mental disorders in ethnic minority areas.

Purpose: Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells. Materials and Methods: Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP. Results: A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice. Conclusion Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.

Objective:To study the role of neonatal panel detection based on next generation sequencing (NGS) combined with multiplex ligation-dependent probe amplification (MLPA) in the etiological differentiation of neonatal hypotonia.Methods:The clinical characteristics and gene test results of newborns with hypotonia as the main clinical manifestation treated at the Department of Neonatology of Jiangxi Provincial Children's Hospital from March 2017 to March 2021 were retrospectively analyzed.Results:A total of 23 children with hypotonia and feeding difficulties diagnosed by gene tests were included. 17 cases (73.9%) had obvious abnormal appearance, and 11 cases (47.8%) had congenital heart disease (atrial septal defect and/or patent ductus arteriosus). Among the 23 infants, 21 were detected by panel gene, 10 by methylation specific MLPA (MS-MLPA) and 4 by MLPA (SMN1 / SMN2). 14 cases of Prader-Willi syndrome, 4 cases of spinal muscular atrophy, 3 cases of congenital myopathy and 2 cases of Schaaf-Yang syndrome were diagnosed. 11 cases died (47.8%), 9 cases had growth retardation (39.1%), 2 cases had normal growth and development (8.7%), and 1 case survived without detailed information (4.3%). Newborns with unknown etiology and low muscle tone are often complicated with abnormal appearance and congenital heart disease. Neonatal panel combined with MLPA is helpful for accurate diagnosis.Conclusions:The detection of neonatal panel combined with MLPA is cheap, and can provide accurate diagnosis for most newborns with unexplained hypotonia in a short diagnosis cycle, which is conducive to the early formulation of clinical decision-making, and guide the treatment, follow-up and genetic consultation of children.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

Objective:To investigate the effect and mechanism of miR-195 regulating FOXK1 gene and PI3K/Akt pathway on stomach adenocarcinoma proliferation, invasion and migration ability.Methods:Public database samples were employed to analyze the expression differences and prognostic significance of miR-195 in stomach adenocarcinoma. After overexpression of mir-195-5p in two cell lines, MGC803 and AGS, altered cell proliferation, invasion, and migration abilities were detected by Alamar Blue, Wound healing, and Transwell assays. The potential target genes and binding sites of miR-195 were predicted by the starBase. Western blot was used to detect the expression levels of foxk1 and phosphorylation sites in the PI3K/Akt pathway of target genes after overexpression of mir-195-5p. A Dual-luciferase reporter assay was used to verify the relationship between mir-195-5p and foxk1. Statistical analyses were performed with IBM SPSS 22 software and R 4.0.3.Results:Our results showed a significant over-expression of miR-195 in the tumor tissues, compared with the paired normal tissues ( P<0.001) , which could inhibit the proliferation and invasion of stomach carcinoma cells and significantly correlated with survival ( P=0.011) . Moreover, our study indicated that miR-195 depressed the expression of FOXK1 and significantly reduced the activation of the PI3K/Akt pathway, which had a negative effect on the proliferation and invasion of stomach carcinoma cells. The phosphorylated Akt (s473 site) expression in the PI3K/Akt pathway was significantly decreased after overexpression of miR-195. Conclusion:Overall, our studies clarify the important function of the miR-195 in the diagnosis and therapy of patients with stomach carcinoma and reveal the FOXK1 and PI3K/Akt pathway regulation by the miR-195, which are of important clinical significance in the differential diagnosis.

Objective To understand the changing resistance proifle ofProteus,Serratia,Citrobacter,Morganella andProvidencia in hospitals across China according to the data from CHINET Antimicrobial Resistance Surveillance Program 2005-2014.Methods Antimicrobial susceptibility was tested by using Kirby-Bauer method or automatic minimum inhibitory concentration determination according to a uniifed protocol.Results A total of 21 663 clinical isolates were collected from January 2005 to December 2014. The proportion ofProteus andSerratia isolates increased with time from 1.41% in 2005 to 2.09% in 2014, and from 0.99% in 2005 to 1.28% in 2014 among all the isolates. No change was found for the proportion ofCitrobacter,Morganella, orProvidencia. Less than 10% of theProteus isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, ceftazidime, cefoxitin, amikacin and tigecycline. Less than 10% of theSerratia isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, amikacin and tigecycline. Less than 20% of theCitrobacter isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, amikacin and tigecycline. Less than 10% of theMorganella isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, amikacin and tigecycline. Less than 20% of theProvidencia isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, cefoxitin and tigecycline.Conclusions The antibiotic resistance ofProteus,Serratia, Citrobacter,Morganella andProvidencia isolates in hospitals across China is growing during the period from 2005 to 2014. Strengthening infection control and rational antibiotic use are effective to slow the growth of drug resistance.