Objective:To investigate the accuracy and feasibility of 3D-printing individualized template-guided and CT-guided 192Ir interstitial brachytherapy in the central recurrent gynecologic tumors by comparing pre-plan and intraoperative physical dosimetric parameters. Methods:This study involved 38 patients with central recurrent gynecologic tumors who underwent 3D printing individual template (3D-PIT)-assisted and CT-guided 192Ir interstitial brachytherapy in the Department of Radiation Oncology of the Peking University Third Hospital from Jan 2018 to Dec 2019.The prescription doses for the target tumor areas were 10-36 Gy to be delivered at 5-6 Gy/fraction for 2-6 fractions.The pre-plan and intraoperative dosimetric parameters were compared, including the minimum prescription doses delivered to 90% and 100% of target volume( D90, D100)and the mean percentage of volume receiving 100% of the prescription doses ( V100). Meanwhile, the doses delivered to 2 cm 3 ( D2 cm 3) of organs at risk (bladders, rectums, and colons) were analyzed.The quality parameters of the brachytherapy were studied, including conformity index (CI), homogeneity index (HI), and external index (EI) of the target volume.Perioperative complications were also observed. Results:A total of 194 treatments were included.During the treatment, 5-13 (median 6) needles were inserted, with a prescription dose of 5-6 Gy per fraction.There were no statistical differences between pre-plan and intraoperative D90, D100, V100, CI, HI, and EI as well as the D2 cm 3 of bladders and colons at risk ( P>0.05). In contrast, for the D2 cm 3 of rectums, the intraoperative dose was slightly higher than the pre-plan dose, showing a statistical difference ( t=-0.335, P=0.027). Conclusions:The 3D-PIT-assisted and CT-guided 192Ir interstitial brachytherapy at a high dose rate is accurate and feasible in the treatment of recurrent gynecologic tumors, meeting the pre-plan dose requirement.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

OBJECTIVE: To investigate the efficacy of image-guided radioactive 125I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121–0.718), lesion volume (HR=2.898; 95% CI=1.139–7.372), D 90 (HR=0.332; 95% CI=0.130–0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136–44.176) and recurrence site (HR=0.358; 95% CI=0.136–0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D 90 (128.5±47.4 Gy), D 100 (50.4±23.7 Gy) and V 100 (86.7%±12.9%). When D 90 ≥105 Gy or D 100 ≥55 Gy or V 100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive 125I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.
Brachytherapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiometry ; Radiotherapy* ; Radiotherapy, Image-Guided ; Recurrence ; Salvage Therapy* ; Tumor Burden ; Uterine Cervical Neoplasms*

Objective To evaluate the outcomes and prognostic factors of image-guided 125I seed implantation for locally recurrent soft tissue sarcoma(RSTS).Methods A total of 60 patients with RSTS who received image-guided 125I seed implantation in Peking University Third Hospital,from September 2002 to December 2015,were retrospectively analyzed.The enrollment criteria: KPS ＞60 points,refused or could not tolerate surgery or radiotherapy,the expecting survival time ＞3 months,relapsed after multiple treatment of soft tissue sarcoma,and underwent CT or ultrasound guided 125 I seed implantation treatment.In all,the median activity of seeds was 25.9×106Bq(range,11.1×106-29.6×106Bq),median number of implanted seeds was 58(range,3-133),and the median D90was 120 Gy(range,36.50-460.97 Gy).The local progression-free survival(LPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.The log-rank test and Cox regression model were used for the univariate and multivariate analyses.Results The median follow-up was 18.75 months(range,1-146).The median OS was 18.5 months(95％CI 13.1-23.9).The 1-,3-and 5-year OS rate were 63.3％,33.0％and 29.5％,respectively.The 1-,3-and 5-year LPFS rate were 72.5％,63.7％and 59.7％,respectively.The general rate of pain relieving was 100％(6/6).8.3％(5/60)presented grade Ⅳskin toxicity.No fatal complications ocurred.The univariate analysis suggested that tumor size,tumor volume,KPS score,D90were prognostic factors of OS and LPFS.The multivariate analysis demonstrated that previous chemotherapy history and distant metastases were independent prognostic factors of survival.Conclusions Image-guided 125I seed implantation for recurrent soft tissue sarcoma is a safe treatment option with high efficacy and low morbidity.Tumor size and D90were the prognostic factors of OS and LPFS.

Objective To compare the differences of gross tumor volume (GTV) and dose distribution between MRI-CT fusion imaging and CT-based imaging and investigate the dose difference in the therapeutic regime.Methods Ten patients diagnosed with primary tumors of the cervical vertebra between 2013 and 2014 were enrolled.Prior to radiotherapy,the imaging data of MRI examination (GE Discovery MR 750 3.0T) were collected,transfered into the Eclipse system and subject to fusion with CT images.GTV delineation,organ at risk (OAR) delineation and dose distribution discrepancy induced by target volume differences were analyzed and statistically compared between the MRI-CT fusion and CT-based images.GTV delineation and dose parameters among different radiologists between two approches were analyzed by analysis of variance (ANOVA) and paired t-test.Non-normally distributed variables were analyzed by Wilcoxon rank-sum test.The reliability of intraclass correlation coefficient (ICC) was assessed.Results The GTVMRI-CT volume was larger compared with the GTVCT volume.The volume overlap index was 0.84±0.17.The cordMRI-CT volume was significantly less than the cordCT volume (P=0.001).For 5 radiologists,the ICCMRI-CT was larger than ICCCT.The DmaxMRI-CT of the spinal cord was (46.00± 1.09) Gy,significantly less than (52.39±1.34) Gy for the DmaxCT(P=0.014).Conclusions It is unlikely to miss the target delineation on MRI-CT fusion imaging.MRI-CT fusion imaging can minimize the discrepancy of interobserver radiologists and cause dosimetric advantages.

Objective To evaluate the efficacy and adverse effects of 125I seeds implantation for pelvic recurrence of cervical cancer (PRCC) after radiotherapy.Methods From July 2005 to October 2015,36 PRCC patients (median 44 years) after radiotherapy in Peking University Third Hospital were enrolled in this retrospective study.All patients underwent 125I seeds implantation under ultrasound or CT guidance.Treatment planning was performed before implantation to estimate the number and activity of 125I seeds.The seed numbers ranged from 10-140 (median:62.5),and the activity ranged from 18.5-29.6 (median:25.9) MBq.Postoperatively,the median dose delivered to 90％ gross tumor volume (D90) was 127.3 Gy.Kaplan-Meier method was used to calculate local progress free survival (LPFS) rate and overall survival (OS) rate,and log rank test and Cox regression were used for univariate and multivariate analyses.Results The median follow-up time was 11.5 months.The local control rate was 88.89％(32/36).The 1-year LPFS rate was 34.9％ and the 1-year OS rate was 52.0％.Thirty-one patients died,of which 22 (70.97％,22/31) died from cancer.Univariate analysis showed that the location of recurrence (x2=5.195),volume of lesion (hazard ratio (HR)=1.012) and D90(HR=0.988) were significantly correlated with LPFS (all P＜0.05).Multivariate analysis showed that the location of the recurrence was significantly related with LPFS (HR =0.215,P＜0.05).The 1-year LPFS rates of pelvic wall recurrence and central recurrence were 41.6％ and 26.7％ (x2 =5.195,P＜0.05),and 1-year OS rates were 54.7％ and 49.5％ (x2 =2.535,P＞0.05),respectively.Vaginal fistula,which may be caused by the treatment,occurred in 1 case.No other sever adverse effects were observed.Conclusions 125I seeds implantation is a safe and effective treatment for PRCC after radiotherapy.With the treatment of 125I seeds implantation,patients with pelvic wall recurrence may achieve better therapeutic effects than those with central recurrence.

Objective To observe the effect of needle warming moxibustion on cognitive dysfunction after stroke. Methods 76 stroke patients with cognitive dysfunction were randomly divided into treatment group (n=38) and control group (n=38). The treatment group received needle warming moxibustion and routine rehabilitation for 4 weeks, while the control group only received routine rehabilitation. They were assessed with Montreal Cognitive Assessment (MoCA) and activities of daily living (ADL) scale before and after treatment. Results The score of MoCA and ADL improved in both groups (P<0.05), and improved more in the treatment group than in the control group (P<0.05) after treatment. Conclusion Needle warming moxibustion could improve cognitive function in patients after stroke and activities of daily living.