Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.

Objective To observe the clinical study of Xiaoaiping tablet combined AP regimen in the treatment of unresectable advance endometrial carcinoma. Methods A total of 268 patients with advance endometrial carcinoma in our hospital were divided into treatment group and control group, 134 cases in each group. The control group was treated by AP regimen and the treatment group was given Xiaoaiping tablet combined AP regimen. The treatment was 3 weeks per course, 4 periods performance, and the 2 year follow-up. After the treatment, the immune index, including IgG, IgA, IgM, CD3+ and CD4+ were detected by a chemical lighting method in the 2 groups. The KPS scores were observed to evaluate the life quality in the 2 groups. During the treatment, the adverse effects of chemotherapy in patients were observated during the treatment. And the survival rates, overall survival and progression-freely-survival were also observed. Results After the treatment, the control rate and efficiency rate were 86.5％ (116/134) and 64.2％(86/134) in treatment group, while the control rate and efficiency rate were 76.9％ (103/134) and 52.2％(70/134) in control group, where there were significantly difference in control rate and efficiency rate (Z values were 3.542 and 3.871, P values were 0.041 and 0.039). After the treatment, the levels of IgG, Ig A, IgM, CD3+ and CD4+ in treatment group were significantly higher than control group (t values were 4.725, 4.930, 4.259, 4.571 and 4.006, P<0.01). After the 1st-4th period of treatment, the KPS scores in treatment group were significantly higher than the control group (t values were 3.124, 3.452, 3.612 and 3.712, P<0.05). After the treatment, the PFS, OS, 1 year survival rate and 2 year survival rate were significantly lower in treatment group than control group (t values were 4.241, 4.421, 3.735 and 3.982, P<0.05). Conclusions The Xiaoaiping tablet combined AP regimen in the treatment of unresectable advance endometrial carcinoma has a good effect, could promote the immune function, decease the adverse effects and prolong the survival time in the patients.

BACKGROUND: Estrogen can promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), but the molecular mechanism is unclear. OBJECTIVE:To study the regulatory effect of estrogen on the osteogenic differentiation of hPDLSCs via Wnt/β-catenin signaling pathway. METHODS: The hPDLSCs were isolated and purified by digestion method combined with limited dilution clone method. Three experimental groups were set as follows: osteogenic induction only (control group); 1×10-7mol/L estrogen with osteogenic induction (estrogen group); and 100 μg/L Wnt3a protein with osteogenic induction (Wnt3a group). Alkaline phosphatase activity was detected at 1, 3, 5, 7 days of osteogenic induction. Western blot was used to detect the expression of Wnt/β-catenin signaling pathway related proteins β-catenin, P-GSK-3β, GSK-3β, CyclinD1 and osteoblast-related proteins Runx2 and OCN after 7 days of osteogenic induction. RESULTS AND CONCLUSION: The activity of ALP in all groups increased with time. The expression level of ALP in the estrogen group and Wnt3a group was higher than that in the control group at 1, 3, 5 and 7 days of induction (P < 0.05), while there was no significant difference between the former two groups (P > 0.05). The western blot results showed that the expression levels of β-catenin, P-GSK-3β, CyclinD1, Runx2 and OCN in the estrogen group and Wnt3a group were higher than those in the control group (P < 0.05), while the expression of GSK-3β was lower than that in the control group (P < 0.05). But there were no differences in the expression of Wnt/β-catenin signaling pathway related proteins and mid-late osteogenic markers between estrogen group and Wnt3a group (P > 0.05). To conclude, estrogen can enhance the osteogenic differentiation of hPDLSCs, and the underlying mechanism is likely to activate the Wnt/β-catenin signaling pathway in activated hPDLSCs exposed to estrogen.

Objective To explore the value of OSCE system combined with intelligent network in-formation platform in clinical skills assessment of obstetrics and gynecology. Methods 112 clinical medi-cal students who participated in the practice of gynecology and obstetrics in Second Military Medical Uni-versity in 2017 were randomly divided into the experimental group (network information OSCE) and the control group (traditional OSCE). The teaching results were evaluated by the questionnaire survey of teachers and students and the examination results as well. The statistical analysis was made with the Chi-square test and the t test respectively. Results According to the questionnaire survey of two skills assessment methods, the satisfaction index of the experimental group was higher than that of the control group in both teachers and students, and the difference was statistically significant (P<0.05). The total time of examination in the experimental group was lower than that of the control group, and the difference was statistically significant (P<0.05). The final total score and the results of case analysis and clinical operation examination of experi-mental group were all higher than those of the control group, but there was no statistical difference (P>0.05). Conclusion OSCE combined with the network information system has an unparalleled advantage in the assessment of the obstetrics and gynecology department. The system will promote clinical education of ob-stetrics and gynecology and the evaluation of the clinical ability of the medical students to a new height, which deserves popularization.

OBJECTIVETo investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC).

METHODSClinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected, and their blood samples were collected accordingly. Genomic DNA was extracted from blood samples. The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method. The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.

RESULTSAllele frequencies of MDR1 2677 G>T/A, ABCG2 421 C>A, 34 G>A, 376 C>T were comparable with previous studies. Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent. Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype, while the differences were not significant. The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012). There were no significant correlations between ABCG2 421 C>A, 34 G>A, 376 C>T and chemotherapy efficacy. No significant correlations were observed between MDR1 2677 G>T/A, ABCG2 421 C>A, ABCG2 34 G>A, ABCG2 376 C>T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.

CONCLUSIONMDR1 2677 G>T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.

ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Adult ; Aged ; Camptothecin ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Treatment Outcome ; Young Adult

ObjectiveTo investigate the clinical features of systemic lupus erythematosus (SLE) patients with fever and find out the related factors.MethodsData was collected by the same methods in the past ten years in fifteen hospitals in Jiangsu province and then the data wereretrospectively analyzed.The potentially possible risk factors of fever in SLE were selected and then analyzed by chi-square test,Wilcoxon rank sum test and Logistic regression analysis.ResultsAll 1762 patients were investigated.Seven hundred and twenty-nine had active fever.Age at hospitalization,initially treated patients,photosensitivity,serositis,nervous system involvement,generalized lymphadenopathy/hepatosplenomegaly,white blood cell count (WBC),haemoglobin (HB),erythrocyte sedimentation rate (ESR),C-reaction protein (CRP),alanine aminotransferase(ALT),albumin(ALB),serum creatinine (Scr),complement C3,anti-dsDNA antibodies positive rate,anti-Sm antibodies positive rate,SLEDAI score and past therapies were factors associatedwith SLE fever.Logistic regression analysis showed that abnormal WBC count (OR=1.396,95％CI 1.114-1.711,P=0.004),CRP(OR=1.005,95％CI 1.002-1.009,P=0.002),ALT(OR=1.003,95％CI 1.001-1.005,P=0.005),Scr (OR=0.997,95％CI0.995-0.999,P=0.007),HB (OR=0.986,95％CI 0.981-0.992,P=0.000),age (OR =0.984,95％ CI 0.974-0.993,P=0.001 ) and past usage of cyclophosphamide (CTX) (OR =0.557,95％CI 0.382-0.813,P=0.002) were correlated with SLE fever.ConclusionFever is one of the most common clinical manifestations of SLE patients.Leucopenia,elevated CRP levels,liver function abnormalities,anemia,younger age are risk factors for SLE fever,while renal impairment and past usage of CTX are protective factors.

Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.

OBJECTIVE: To explore the reversal effect of pioglitazone (PIO) on multidrug resistance in K562/ADR cells and its mechanism. METHODS: The proliferation inhibition rate, half inhibition concentration (IC) and drug-resistance reversal multipe were detected and the curve of proliferation inhibition rate was drawn by MTT assay, the transcription of PPARγ, CYP2C8 and CYP2J2 genes was detected by RT-PCR; the expression of PPARγ, CYP2C8 and CYP2J2 proteins was detected by Western blot. RESULTS: The IC of PIO on K562 and K562/ADR cells for 60 h was 326.7 μmol/L and 349.1 μmol/L respectively. The reversal multiple of 30 μmol/L PIO on ADR-resistance of K562/ADR cells was 6.4. After treatment of K562/ADR cells with PIO, the transcription of CYP2C8 and CYP2J2 and the protein expression of CYP2C8 and CYP2J2 significantly decreased, the transcription of PPARγ gene and the expression of PPARγ protein were not changed. CONCLUSIONS Pioglitazone can reverse the adriamycin-resistance in K562/ADR cells that is closely related to the decrease of protein expression of CYP2C8 and CYP2J2. Pioglitazone is an effective multidrug resistance reversal agent for tumors.
Doxorubicin ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; K562 Cells ; Pioglitazone

OBJECTIVE: To investigate the expression of autophagy-related protein Beclin-1 and microtubule-associated protein 2 light chain 3 (LC3Ⅱ) in periodontal ligament cells in orthodontic tooth pressure areas. METHODS: Sixty male SD rats were randomly divided into a blank control group and nine experimental groups. In the experimental groups, 0.392 N orthodontic force was used to move the first right upper molars for 15 min, 30 min, 1 h, 2 h, 4 h, 12 h, 1 d, 3 d, or 7 d. The blank control group did not receive any treatment. The rats were euthanized. Changes in the morphology of the periodontal membrane in the pressure areas were observed through hematoxylin and eosin (HE) staining. The expression levels of Beclin-1 and LC3Ⅱ were detected by immunohistochemical staining, and tartrate-resistant acid phosphatase (TRAP) staining was performed for the counting of osteoclasts. RESULTS: The HE stains showed that the hyalinization of the periodontal ligament appeared in the pressure areas after 1 day of exertion and was gradually aggravated. The immunohistochemical stains showed that the expression levels of Beclin-1 and LC3Ⅱ in the experimental groups gradually increased, peaked after 1 h, and then gradually decreased. The expression levels peaked again after 1 d, then decreased to baseline levels at 7 d of exertion. Beclin-1 and LC3Ⅱ were expressed in the osteoclasts. The TRAP stains indicated that the number of osteoclasts started to increase after 1 day. CONCLUSIONS Autophagy may participate in the process of periodontal ligament reconstruction in orthodontic tooth pressure areas by mediating the hyalinization of periodontal ligament and affecting the biological effects of osteoclasts.
Animals ; Autophagy ; Beclin-1 ; metabolism ; Male ; Microtubule-Associated Proteins ; metabolism ; Osteoclasts ; Periodontal Ligament ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tooth Movement Techniques

OBJECTIVE: To explore the changes of autophagic activity after resistance of U266 cells to bortezomib (Bor) and its mechanisms. METHODS: The proliferation inhibition rate, 50% inhibitory concentration (IC), drug-resistance coefficient, drug-resistance reversed multiple by 3-methyladenine (3-MA) in U266 and U266/Bor cells treated with Bor were detected and calculated by using MTT method, then the proliferation inhibition curve was drawed. The Western blot was used to detect the expression of LC3-I, IC3-II, p-mTOR, Beclin-1, ATG5 and ATG7 proteins. RESULTS: The Bor showed the its proliferation inhibition effect on U266 cells and U266/Bor cells, IC of Bor on U266 and U266/Bor cells on 24 hours were 35.7 nmol/L and 526.5 nmol/L respectively; the drug-resistance coefficient was 14.7; the drug-resistance reversed multiple by 3-MA was 2.7. The expression of LC3-II, Beclin11, ATG5 and ATG7 in U266/Bor cells was higher than that in U266 cells; after the treatment with Bor for 24 h, the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266 cells all decreased, as compared with levels before treatment; while the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266/Bor cells were higher than those before treatment. There were no significant difference of p-mTOR expression among U266, U266+Bor, U266/Bor, U266/Bor+Bor cells. CONCLUSION The increase of autophagy closely relates with resistance of U266 cells to bortezomib, moreover with up-regulation of Beclin-1, ATG5 and ATG7 expression.
Apoptosis ; Autophagy ; Beclin-1 ; Bortezomib ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Humans