Effect of CCNU on survival rate of objective remission and duration of free interval in patients with malignant brain glioma—Final evaluation

The effect of CCNU on three clinical parameters was measured in patients with malignant brain gliomas, operated and treated by radiation therapy (5500–6000 rad).From 111 selected patients included in the first trial (No. 26741) 81 were avialable for the final evaluation.Four questions were answered by this study:

• 1.(a) Free interval can be measured in a selected group of patients with malignant brain glioma.
• 2.(b) CCNU (mean dosage actually given was over 100 mg/m² once every 6 weeks) does not prolong the free interval.
• 3.(c) Objective remission was observed in 8 out of 27 patients where this parameter was evaluable. The duration of the remission ranged from 3 to over 14 months.
• 4.(d) The median survival of patients who received CCNU only after relapse was 22.5 weeks from the recurrence and 62 weeks from the operation; the figures for patients treated earlier with CCNU were 11 and 43 weeks. These differences are significant at respectively 2 and 7% levels.

Only survival time was measured in the second trial (No. 26742), it was 31 weeks in patients treated with CCNU and 21.5 in the control group. Although only 19 patients were evaluated, the difference is significant at 1% level.Combined results of both trials suggest so far that: CCNU prolongs the total survival time, produces objective remission in about 30% of cases and that it should be administered only after relapse, at least in patients with free interval.     

Effect of selective uterine artery embolization on symptomatic uterine fibroids

Objective： To evaluate the outcomes of selective uterine artery embolization （SUAE） in treatment of symptomatic uterine fibroids using Color Doppler ultrasonography （CDUS）. Methods： As the procedure SUAE for fibroids, prospective data of the initial 65 consecutive women treated from March 2007 to September 2009 were collected. The follow-up period from 1 week to 30 months, using questionnaires, we investigated the fibroid-related physical and psychological symptoms, and the cumulative rates of symptom control, gynecologic interventions, and complications. The volumes of uterine and uterine fibroids were calculated by CDUS pre- and post-SUAE for 6 months. And we tested the levels of internal hormone including FSH, LH and E2 before and after SUAE for 3, 6 months. Results： SUAE was performed successfully in all patients. There was no peri-operative morbidity in all procedures. Compared with pre-SUAE volumes of uterine [（322± 12） cm^3] and uterine fibroids [（125±46） cm^3], their volumes in post-SUAE were （144±72） cm^3 and （51 a：l 1） cm^3 （P〈0.01）, and reduction rate was 58% and 61%, respectively. At 3, 6 months after SUAE, levels of FSH, LH, and E2 were not decreased than that of in pre-SUAE （P〉0.05）. After SUAE for 24 months, the fibroids related physical and psychological symptoms such as bleeding, pain and quality of life were significantly improved （P〈0.01）. 90.8% （59/65） women had resolution of symptoms and no significant post-procedural symptoms. Parts of patients discharge necrotic fibroids. 86% （34/40） complications were minor, requiring no therapy. 9.2% （6/65） had significant post-procedural symptoms, requiring therapy in hospital or out-patient department. Conclusion： SUAE contributes to a long-term significant improvement of all investigated uterine fibroid-related symptoms and markedly improves women＇s health-related quality of life. SUAE that no impair on changes of internal hormone, under suitable conditions, represents an attractive alternative to hysterectomy for the treatment of symptomatic fibroids and is a minimally invasive, new method of good clinical prognosis. CDUS is an effective to investigate the outcome of SUAE.     

肺癌相关miRNAs研究进展

肺癌的发生发展为复杂的多基因事件,microRNAs（miRNAs）参与其中并发挥重要作用。miR-NAs为一系列长约19-25nt的内源性非编码微小RNA,可抑制靶基因转录或蛋白翻译从而沉默靶基因的表达。部分miRNAs在肺癌组织中表达上调,并证明可负性调节抑癌基因。亦有部分miRNAs在肺癌组织中表达下调,被认为是抑癌基因且其中一部分也已得到证实,在临床潜在应用方面,目前研究证实miR-101可发挥放疗增敏效应,而miR-134、miR-379与miR-495或有助于指导肺癌化疗用药的选择。通过回顾最新文献,本文对肺癌高度相关的miRNAs及其靶基因进行了总结,并在生物学效应、潜在靶基因、基因诊断、治疗、预测预后等方面进行探讨。     

Multicenter cross‐sectional observational study of antibiotic resistance and the genotypes of Propionibacterium acnes isolated from Chinese patients with acne vulgaris

Antibiotics are widely applied in management of acne vulgaris, which raises the issue of antibiotic resistance. Due to improper application and supervision of antibiotics, antibiotic resistance has become a serious problem in China. So, the efficacy of antimicrobial therapy in acne is unclear without an objective monitor of antibiotic resistance of Propionibacterium acnes. This cross‐sectional, multicenter observational study is aimed at understanding the status of antibiotic resistance in P. acnes, investigating the measures of acne management in China and analyzing the genotypes of antibiotic‐resistant strains of P. acnes. Altogether, 312 strains of P. acnes were collected from patients in five medical centers across central China after reviewing the corresponding medical history in detail. The samples underwent antibiotic susceptibility assays by agar dilution method with a total of 11 classes of antibiotics being tested. The antibiotic‐resistant strains were screened and further analyzed by investigation of the genotypes regarding 23S rRNA, 16S rRNA and erm(X). The predominant resistance occurred in macrolides and lincomycin with an overall resistance rate of 47.8%. The resistance to tetracyclines was scarce with only two cases identified. The emergence of minimum inhibitory concentration elevation for tetracyclines is associated with its application history (P < 0.005). The genotypes of the reported macrolide–lincosamide–streptogramin B resistance strains were also spotted in Chinese subjects while other resistance determinants may also exist. The tetracyclines have been proved to be vastly susceptible while macrolides and lincomycin face a serious resistance status in China.     

Circular RNAs: The crucial regulatory molecules in colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Recent studies have shown that circular RNAs (circRNAs) play critical roles in the pathogenesis and progression of CRC. CircRNAs are a special class of endogenous non-coding RNAs (ncRNAs) that harbor covalently closed ring structure with high conservation and stability, which are expressed in a tissue- and developmental-stage-specific manner. A growing body of evidence suggests that circRNAs are abnormally expressed in CRC tissues, cell lines and plasma, and are closely linked with CRC clinical malignant features. CircRNAs participate in various biological processes of CRC cells, including cell proliferation, apoptosis, senescence, migration and invasion and so on, through acting as “microRNA (miRNA) sponges”, binding to protein and even translating protein. In the present review, we systematically introduce the CRC-related circRNAs and their functional mechanisms, as well as the potential applications for CRC diagnosis and prognosis.     

Efficacy and Safety of Befotertinib (D-0316) in Patients With EGFR T790M-Mutated NSCLC That Had Progressed After Prior EGFR Tyrosine Kinase Inhibitor Therapy: A Phase 2, Multicenter,Single-Arm,Open-Label Study

IntroductionBefotertinib (D-0316) is a novel, third-generation EGFR tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.MethodsThis was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression after prior first- or second-generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156.ResultsA total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75–100 mg), respectively. At data cutoff (August 15, 2021), independent review committee–assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%–72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%–61.5%) in cohort A and 65.9% (95% CI: 60.1%–71.3%) in cohort B. The median investigator-assessed progression-free survival was 11.0 (95% CI: 9.6–12.5) months in cohort A and 12.5 (95% CI: 11.1–13.8) months in cohort B. The median independent review committee–assessed progression-free survival in cohort B was 16.6 (95% CI: 15.0–not evaluable [NE]) months. The intracranial ORR was 26.7% (95% CI: 7.8%–55.1%) in cohort A by investigator assessment, while 57.1% (95% CI: 34.0%–78.2%) and 55.9% (95% CI: 37.9%–72.8%) in cohort B by investigator and independent review committee assessment, respectively. The median investigator-assessed intracranial progression-free survival was 16.5 (95% CI: 8.6–NE) months in cohort A, while the median intracranial progression-free survival was not evaluable in cohort B due to immature data regardless of investigator or independent review committee assessment. and NE (95% CI: 13.8–NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A and in 29.3% and 10.0% of patients in cohort B, respectively.ConclusionsBefotertinib of 75 to 100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second-generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).     

Prediction of prolonged resolution of chylous ascites after radical D3 resection for colorectal cancer: A population-based experience from a high-volume center

AimThis study was aimed to analyze the incidence, risk factors, and management of chylous ascites (CA) after radical D3 resection for colorectal cancer, and to construct a predicting nomogram for prolonged resolution of CA.MethodConsecutive colorectal cancer patients who underwent radical D3 resection were included. Logistic analysis was used to identify risk factors of postoperative CA, as well as prolonged CA resolution. A predictive nomogram for prolonged resolution of CA was developed and validated internally.ResultsAmong 7167 patients included, 277 (3.8%) patients developed CA. Logistic regression analysis demonstrated that laparoscopic operation (OR 1.507; P = 0.017) and tumors fed by the superior mesenteric artery (SMA, OR 2.456; P < 0.001) were independent risk factors of postoperative CA following radical D3 surgery for colorectal cancer. Open operation (OR 0.422; P = 0.027), drainage output on the first day of treatment (OR 1.004; P = 0.016), time to oral intake (OR 1.273; P = 0.042), and time to onset (OR 1.231; P = 0.024) were independently associated with prolonged resolution of postoperative CA (≥7 days). A predictive nomogram for prolonged CA resolution was developed with a C-index of 0.725.ConclusionThe incidence of CA after radical D3 surgery of colorectal cancer was 3.8%. Open operation, drainage output on the first day of treatment, time to oral intake, and time to onset were independently associated with prolonged resolution of postoperative CA. A nomogram may assist in tailored treatment decision-making and counseling patient with treatment strategies.