Objective To evaluate the predictive value of a dose-surface histogram (DSH) for radiation cystitis (RC) in patients with cervical cancer. Methods We retrospectively included 190 patients with cervical cancer who underwent image-guided radiotherapy (IGRT) from the HIS system of The First Affiliated Hospital of Hebei North University from May 2013 to May 2023. The patients were divided into test group (n = 100) and control group (n = 90). The dose distribution in the bladder was evaluated by using a DSH for the test group and using a dose-volume histogram (DVH) for the control group. Receiver operating characteristic curves were used to evaluate the predictive value of DSH for RC in comparison with DVH. Results There were no significant differences in baseline data and RC incidence between the two groups (all P＞0.05). All evaluation indicators were significantly different between DSH and DVH (all P＜0.05). The predictive value of S₄₅ and V₄₅ for the incidence of grade-I, -II, and -III RC was low (all P＜0.05). The predictive value of S₅₀ and V₅₀ for the incidence of grade-I, -II, and -III RC was moderate (all P＜0.05). S₅₅−S₅₇ and V₅₅−V₅₇ showed high value for predicting the incidence of grade-I, -II, and -III RC (all P＜0.05). Conclusion DSH shows basically the same predictive value for the incidence of RC caused by IGRT in cervical cancer as DVH, which is expected to become a new tool for evaluating radiotherapy plans.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

Objective:To investigate the clinical safety and efficacy of tirofiban in the treatment of hemiplegic stroke warning syndrome.Methods:Patients with hemiplegic stroke warning syndrome admitted to Jining First People's Hospital without receiving intravenous thrombolysis from January 2018 to May 2020 were enrolled retrospectively. Some patients were given tirofiban intravenous infusion for at least 24 h in acute phase, then received oral antiplatelet therapy (tirofiban group); some only received aspirin+ clopidogrel dual antiplatelet therapy (control group). The primary endpoint was muscle strength at the paralytic side and National Institutes of Health Stroke Scale (NIHSS) score at day 7 after onset. The secondary endpoint was the modified Rankin Scale (mRS) score at 3 months after onset, and ≤2 was defined as good clinical outcome. The safety endpoint was the bleeding events during treatment. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results:A total of 30 patients with hemiplegic stroke warning syndrome were enrolled, including 19 (63.3%) in the tirofiban group and 11 (36.7%) in the control group. There was no significant difference in baseline clinical data between the two groups, and no drug-related bleeding complications occurred during treatment. The muscle strength at paralytic side and NIHSS score at day 7 after onset, NIHSS score at discharge and good clinical outcome rate at 3 months in the tirofiban group were significantly better than those in the control group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that tirofiban was an independent protective factor for good outcome after adjusting the NIHSS score at the beginning of treatment (odds ratio 0.040, 95% confidence interval 0.040-0.449; P=0.009). Conclusions:Tirofiban is safe and effective in the treatment of patients with hemiplegic stroke warning syndrome in acute phase. It can effectively block the progress of the disease, improve the outcome of patients, and will not increase the risk of bleeding.

Objective To investigate the correlation between late-onset sporadic parkinson's disease(PD) and single nucleotide polymorphism (SNP) of autophagy-related genes 7 (Atg7) rs2606757 (6+1196A/T)in Han Chinese population.Methods Totally 124 patients with late-onset sporadic PD(the PD group)and 105 age-and sex-matched healthy individuals(the control group)were enrolled in this study.The SNP of Atg7 rs2606757 was detected by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).After gene sequencing for the detection of allele and genotype frequencies distribution and testing Hardy-Weinberg equilibrium,the differences in Atg7 rs2606757 genotype and allele frequency were compared between PD group and control group and between males and females.Results The frequency of AA genotype was statistically significantly lower in the PD group[34.7％(43/124)]than in the control group[53.3 ％ (56/105)](x2 =8.063,P=0.005,OR =0.465,95％ CI:0.273-0.791).In men's PD group versus men's control group,AA genotype of the Atg7 rs2606757 showed a lower frequency for late-onset sporadic PD[33.3 ％ (23/69)vs.53.2 ％ (33/62),x2 =5.280,P =0.022,OR =0.439,95 ％ CI:0.217-0.891].Logistic regression analysis indicated that the AA genotype frequency distribution of Atg7 rs2606757 showed a significant difference between PD and control groups (OR =2.210,95％ CI:1.289-3.789,P =0.004).Conclusions The higher frequence of AA genotype at Atg7 rs2606757 only in males might be associated with the decreased risk of late-onset sporadic PD.

Objective To explore the association of ubiquitin-specific proteases 24 (USP24) gene polymorphisms with susceptibility to sporadic Parkinson's disease (PD) in the Han Guangdong population. Methods From August, 2006 to January, 2014, single nucleotide poly-morphisms (SNPs) of rs12138592 and rs6671533 in the intron region of USP24 were genotyped in 200 patients with sporadic PD and 200 healthy controls using the SNaPshot technique. Results There was significant difference in the allele and genotype frequency of rs12138592 between the patients and the controls (P<0.01), and no significant difference was found in the allele and genotype frequency of rs6671533 (P>0.05). Conclusion The SNP of rs12138592 in the intron region of USP24 is associated with the susceptibility to sporadic PD in the Han Guangdong population, and the A allele may contribute a protective roles to PD.

Objective To evaluate the effect of targeted monitoring and comprehensive intervention measures on reducing the occurrence of catheter-associated urinary tract infection(CAUTI)in patients in non-intensive care unit(Non-ICU).Methods In quarter 4 of 2015,patients with indwelling urinary catheter in clinical departments were conducted a baseline survey(before intervention),risk factors for CAUTI in patients were analyzed,targeted monitoring programmes and comprehensive intervention measures were initiated in 2016(after intervention),incidence of CAUTI before and after intervention was compared.Results After taking intervention measures,hand hygiene compliance rate increased from 78.51%in quarter 4 of 2015 to 92.99%in quarter 3 of 2016 and 90.73%in quarter 4 of 2016(x2=7.342,3.998,respectively,both P<0.05),the correct disposal rate of patients' urinary catheterization system increased from 72.83%in quarter 4 of 2015 to 95.44%in quarter 4 of 2016(x2=30.267,P<0.05).A total of 12 067 patients with indwelling urinary catheter were monitored,incidence of CAUTI dropped from 1.03%(24/23 313)in quarter 4 of 2015(before intervention)to 0.53%(14/26 595)in quarter 4 of 2016(after intervention),difference was statistically significant(x2=4.126,P=0.042).Conclusion Improving the quality of urinary catheterization system in patients with indwelling catheter through targeted monitoring can effectively reduce the incidence of CAUTI in patients in Non-ICU.

Objective To investigate the association between rs14016 (19 +31C/T) polymorphisms of autophagy-related genes 7 (Atg7) and Parkinson's disease (PD) in Han population in China.Methods Totally 123 patients with Parkinson's disease (PD) (case group) and 101 synchronized health controls (control group) were selected from Chinese Han population between January 2013 and July 2016.A single nucleotide polymorphism (SNP) of rs14016 of Atg7 gene was detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.After gene sequencing for genotyping and detection of alleles,genotype and allele frequency distributions were analyzed in the two groups.Results The frequency distributions of TT genotype and T alleles were 17.9％ (22/123) and 41.1％ (101/246) in the case group,and 5.9％ (6/101) and 31.2 ％ (63/202) in the control group,respectively.The difference in genotype frequencies between the two groups was statistically significant (x2 =7.236,P =0.007,OR =3.01,95 ％ CI:1.27-7.14).The frequencies of T and C alleles were 41.1％ (101/246) and 58.9％ (145/246) respectively in the case group,and 31.2％ (63/202) and 68.8％ (139/202) in the control group (x2 =4.655,P=0.031,OR=1.32,95 ％CI:1.02-1.70),with the statistically significant difference in the allele.The TT genotype of rs14016 showed statistical significance between the two groups by logistic regression analysis (OR=3.40,95％CI:1.32-8.80,P=0.012).Conclusions The T allele and TT genotype at the rs14016 of Atg7 gene might be associated with PD,and might increase the risk for suffering from PD,which is worthy of further fully researches.

Background Epithelial-mesenchymal transition (EMT) is one of the pathogenesis mechanisms of posterior capule opcification (PCO).Studying EMT is of important significance for the prevention and treatment of PCO.However,EMT model is lack.Objective This study was to establish an in vitro EMT model for the study of human PCO.Methods In vitro mimic cataract enucleation was performed on 40 donor eyes,including anterior capsulorhexis,nucleus hydroexpression,and aspiration of lens fibers.The capsular bag of lens was dissected free during the surgery and pinned flat on a plastic culture dish with DMEM/F12 supplemented containing 10％ fetal bovine serum for 4 weeks.The proliferation of LECs on the capsular bag was observed by phase-contrast and dark-field microscope in 0,3,7,14 and 28 days after culture.The capsular bag tissues were collected in cultured 0,3,7 and 28 days for the preparation of sections and hematoxylin-eosin stain,and the growth and morphology of LECs were examined with optical microscope.The expression and location of α-SMA,E-cadherin and Vimentin were assessed by immunochemistry.The expression levels of α-SMA,E-cadherin and Vimentin mRNA and proteins were detected by using real-time fluorescnce quantitative PCR and Western blot in different time points.Results No LECs were seen on the uncultured capsular bag.LECs appeared in cultured day 3 on the periphery capsular bag and grew toward the center and covered the posterior capsule 7 days after cultured,with a cobblestone-like appearance.Wrinkles occurred and extended gradually along with the enhancement of bag tension.Immunochestry showed that the expression intensity of E-cadherin in the capsular bag gradually weakened,and that of α-SMA or Vimentin was gradually enhanced during the culture duration.The relative expression levels of E-cadherhin mRNA at 0,3,7,14 and 28 days after culture were 3.35±0.13,1.47±0.20,1.13±0.14,1.00±0.85 and 0.23±0.03,and relative expression levels of Vimentin mRNA were 1.00 ± 0.73,1.05 ± 0.14,2.24 ± 0.43,2.84 ± 0.34 and 8.57 ± 0.40,and those of α-SMA mRNA were 1.00 ± 0.06,2.68 ± 0.28,4.24 ± 0.05,2.05 ± 0.90 and 15.30 ± 0.19,showing significant differences among different time points (E-cadherhin mRNA:F =23.430,P =0.000;Vimentin mRNA F =8.915,P =0.002;α-SMA mRNA:F =103.500,P =0.000),with the lowest expression levels in the E-cadherhin mRNA and the highest expression levels in the Vimentin mRNA and α-SMA mRNA at 28 days during the culture period (all at P＜0.01).The gray values of E-cadherin protein expression were 1.443 ± 0.017,1.023 ± 0.003 and 0.568 ± 0.018,and those of Vimentin protein were 0.565±0.012,1.156±0.007 and 1.241±0.009,and those of α-SMA protein were 0.195±0.045,0.693±0.036 and 1.501±0.005 at 0,3 and 28 days,with significnant differences among various time points (E-cadherin:F =2 787.000,P =0.000;Vimentin:F =4 488.000,P =0.000;α-SMA:F =1 173.000,P =0.000).The expression levels were significantly declined in E-cadherhin protein and elevated in Vimentin and α-SMA proteins at 3 and 28 days after culture in comparison with before culture.Conclusions A novel in vitro EMT model of LECs is established in this study.This model can mimic a natural EMT procedure after extracapsular cataract enucleation and therefore is a useful model for the further research of the mechanism and prevention and treatment of PCO.

Objective To analyze and compare the pathological changes of lung tissue in mice infected with the novel H7N9 influenza virus and 2009 pandemic H1N1 influenza virus, respectively, and to preliminarily study the mecha-nisms of acute lung injury induced by those virus infection .Methods SPF 6-week old BALB/c mice ( body weight 18-20 g, male∶female=1∶1) (n=3 in each subgroup) were intranasally infected with H7N9 virus and H1N1 virus, respec-tively.The behavior and survival time of mice after virus infection were observed and the survival rates were analyzed .The heart, liver, spleen, lung, kidney, intestines, and brain were collected at indicated time points for histopathological exami-nation using H&E staining .The distribution of virus antigen was detected by immunohistochemistry .The neutrophil infiltra-tion was also observed .The correlation of lung injury with virus replication and host immune responses was analyzed .Re-sults The lung and spleen injury of mice infected with H 7N9 virus was slighter and their survival rate (100%) was high-er than those of mice infected with H1N1 virus.The damages of the lung and spleen in H1N1virus-infected mice were more severe than that in H7N9 virus-infected mice, and all the 10 mice in this group died within 9 days after virus inoculation . The distributions of both the virus antigens were mainly in the bronchial epithelial cells , a few stromal cells and alveolar ep-ithelial cells .The levels of virus replication in the two groups were not significantly different .There were more intense neu-trophil infiltration in the lung and inflammatory response in the H 1N1 virus-infected mice than those in the H7N9 virus-in-fected mice .Conclusions There are some differences of the pathological characteristics and extent of lung injury in the mice infected with H7N9 virus and H1N1 virus, respectively.The virus replication is a precipitating factor but not the deci-sive factor of the lung injury , and there is a close relationship between the host immune responses and acute lung injury .