地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

Primary and recurrent regional metastases for lateralized oral cavity squamous cell carcinoma

ObjectivesMap regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence.Materials and methodsRetrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997–2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression.ResultsRegional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2–3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9–9.3; T4 vs. T1: HR 2.3, 95% CI 1.2–4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2–16.1), upper alveolus (HR 3.2, 95% CI 1.0–4.7) or with LVI (HR 2.0, 95% CI 1.0–3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases.ConclusionsFor lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3–4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.     

Silver Diamine Fluoride Protocol for Reducing Preventable Dental Hospitalisations in Victorian Children

IntroductionThis study was designed to assess whether a dental caries management protocol combining a single application of 38% silver diamine fluoride (SDF) with comprehensive oral health education will successfully divert high-risk children from dental treatment under dental general anaesthesia (DGA), arrest active caries in primary teeth, and improve parent-reported child oral health–related quality of life (OHRQoL).MethodsChildren aged 2 to 10 years, who attended two public dental agencies in Victoria, Australia, and were unable to tolerate restorative treatments in the clinic setting, elected to participate in either a 38% SDF intervention protocol or, alternatively, referral for DGA. Follow-up examinations were completed at 6 months to assess caries progression, decayed missing filled tooth index, PUFA index (pulpal involvement, ulceration, fistula, abscess), DGA referral rates, and OHRQoL (Early Childhood Oral Health Impact Scale [ECOHIS]).ResultsOf the total sample, 89.5% of children (n = 102) [mean (SD) age, 4.1 (1.0) years] with 401 active carious lesions elected to participate in the 38% SDF protocol; 10.5% (n = 12) of parents opted for referral for treatment under DGA. The proportion of active caries subsequently arrested at follow-up (number of arrested lesions/number of lesions treated) was 0.78 (95% CI, 0.69 to 0.87). There was an 88% reduction in referrals for DGA in eligible children over the 6-month period. The 38% SDF intervention group showed a significant improvement in ECOHIS scores at follow-up (P < .001).DiscussionAdoption of the 38% SDF intervention protocol resulted in a significant reduction in the rate of preventable dental hospitalisations. Most parents opted against referral for DGA. Parent-reported OHRQoL for children improved significantly.     

Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.     

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Survival in node-positive early oral squamous cell carcinoma: sentinel node biopsy versus elective neck dissection

Patients undergoing sentinel node biopsy (SLNB) for early oral squamous cell carcinoma (OSCC) who harbour occult metastases (pN+ve) may be at greater risk of mortality due to prolonged overall treatment times than those identified as pN+ve on elective neck dissection (ELND). A retrospective comparative survival analysis was therefore undertaken to test this hypothesis. Patients were identified from the South Glasgow multidisciplinary team (MDT) database. Group 1 comprised 38 patients identified as pN+ve, or who were false negative, on sentinel lymph node biopsy (SLNB). Group 2 comprised 146 patients staged pN+ve on ELND. The groups were compared with the Kaplan Meier method and Cox proportional hazards model. In addition, a matched-pair analysis was performed. A unique and specifically designed algorithm was deployed to optimise the pairings. No difference in disease-specific or overall survival was found between the groups. Patients undergoing SLNB as the initial neck staging modality in early OSCC and are identified as pN+ve do not appear to be at a survival disadvantage compared with those staged with ELND.