基于深度学习的CBCT下颌神经管自动分割算法综述

下颌神经管是非常重要的下颌骨结构,许多下颌手术都需要了解下颌神经管的位置和走向。目前,锥形束计算机断层成像(Cone beam computed tomography, CBCT)是主流的术前影像检测手段。但是人工从CBCT图像中识别、分割出下颌神经管是费时费力的一项工作,基于深度学习的自动分割技术成为当前的研究热点。本文对该领域的技术进展和研究现状进行了梳理,将近年来利用深度学习实现下颌神经管自动分割的算法进行了分类、汇总和比较,并讨论了该领域的未来发展方向。

加味茵陈蒿汤联合熊去氧胆酸治疗原发性胆汁性胆管炎的临床疗效及对FGF19的影响

目的评价加味茵陈蒿汤联合熊去氧胆酸治疗原发性胆汁性胆管炎的临床疗效及对血清FGF19的影响。方法将64例肝胆湿热兼瘀血阻络型原发性胆汁性胆管炎患者随机分为治疗组和对照组,每组32例。治疗组给予加味茵陈蒿汤联合熊去氧胆酸治疗,对照组给予熊去氧胆酸治疗。两组疗程均为12个月,观察中医证候积分、生化学应答率、肝脏生化指标、血清FGF19的变化情况。结果①治疗后,治疗组、对照组的生化学应答率分别为87.5%、62.5%,组间差异有统计学意义(P<0.05);②治疗后,治疗组血清ALT、AST、GGT、ALP水平均较对照组下降,差异有统计学意义(P<0.05);③治疗后,治疗组中医证候积分低于对照组,差异有统计学意义(P<0.05);④治疗后,治疗组血清FGF19水平较对照组升高,差异有统计学意义(P<0.05)。结论加味茵陈蒿汤联合熊去氧胆酸治疗肝胆湿热兼瘀血阻络型原发性胆汁性胆管炎,能够有效提高生化学应答率,可改善血清ALT、AST、GGT、ALP水平及中医证候积分,提高血清FGF19水平。

丁酸梭菌的生物学功能及其在水产养殖中的应用研究进展

丁酸梭菌作为一种新型的微生物饲料添加剂,在畜禽养殖中的研究及应用较多,但在水产养殖中的应用研究仍处于起步阶段。丁酸梭菌在水产养殖动物中具有维持消化道微生态平衡、改善肠道上皮组织的健康状况、提高机体免疫力和促进营养物质的消化吸收等功能。本文主要对丁酸梭菌的生物学功能及其在水产养殖中的应用研究现状进行综述,并指出其作为水产饲料添加剂在应用中存在的问题,同时对其未来发展前景进行了展望。

Pulsatile gonadotropin-releasing hormone therapy is associated with earlier spermatogenesis compared to combined gonadotropin therapy in patients with congenital hypogonadotropic hypogonadism

Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism （CH H）. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH： twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months （range： 12-27 months） for the GnRH group and 28.7 ± 13.0 months （range： 12-66 months） for the HCG/HMG group. The median time to first sperm appearance was 6 months （95% confidence interval [CI]： 1.6-10.4） in the GnRH group versus 18 months （95% Ch 16.4-20.0） in the HCG/HMG group （P〈 0.001）. The median time to achieve sperm concentrations 〉5 x 106 m1-1 was 14 months （95% Ch 5.8-22.2） in the GnRH group versus 27 months （95% Ch 18.9-35.1） in the HCG/HMG group （P 〈 0.001）, and the median time to concentrations 〉10 x 106 m1-1 was 18 months （95% Ch 10.0-26.0） in the GnRH group versus 39 months （95% CI unknown） in the HCG/HMG group. Compared to the GnRH group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of 〉4 ml, 〉8 ml, 〉12 ml, and 〉16 ml. Sperm motility （a ＋ b ＋ c percentage） evaluated in semen samples with concentrations 〉1 × 106 ml-1 was 43.7% ± 20.4% （16 samples） in the GnRH group versus 43.2% ± 18.1% （153 samples） in the HCG/HMG group （P= 0.921）. Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group （8.3 ±4.6 vs 16.2 ± 8.2 nmol 1-1, P 〈 0.001）. Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.

Targeting both sides of the GDF15-GFRALRET receptor complex:A new approach to achieve body weight homeostasis

Obesity is a chronic,complex disease,which is associated with several comorbidities,including diabetes mellitus,hypertension,and cardiovascular diseases.It is estimated that the prevalence of obesity among both adults and children nearly tripled between 1975 and 2016,highlighting a huge unmet treatment need.However,the currently available antiobesity drugs have serious side effects,which limit their long-term use.The finding that the newly-identified brain GDF15-GFRAL-RET receptor signaling complex is involved in stress/disease-induced anorexia will certainly impact our knowledge of body weight homeostasis under healthy and disease conditions.Based on this breakthrough,a new class of GFRAL/RETbased drugs is highly anticipated for the treatment of obesity,as well as cancer-induced cachexia.

基于“肝脏-胆汁酸-肠道微生态”的苍菊清肝方治疗非酒精性脂肪肝的机制研究

目的:探索高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)模型小鼠的“肝脏-胆汁酸-肠道微生态轴”失衡的病理机制,验证苍菊清肝方对“肝脏-胆汁酸-肠道微生态轴”失衡的调节,进一步阐明苍菊方治疗NAFLD的机制。方法:32只雄性SPF级SD大鼠随机分为空白组(N,n=5)和高脂饮食组(HFD,n=27)。空白组5只给予普通饲料,高脂饲料组以高脂饲料(胆固醇1%,猪油10%,蔗糖20%)喂养,诱导NAFLD模型。饲养8周后,高脂饮食组造模成功的25只大鼠再随机分为模型组(HFDM,n=5)、益生菌组(YSJ,n=5)、苍菊方高剂量组(CJFH,n=5)、苍菊方中剂量组(CJFM,n=5)、苍菊方低剂量组(CJFL,n=5)。利用全自动生化仪检测各组大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、总胆固醇(TC)含量。HE染色观察大鼠肝组织病变程度以及脂质沉积情况。用Illumina高通量测序法,对大鼠粪便样本总DNA的16Sr RNA的V3~V4区进行基因测序以及生物信息学分析。结果:与空白组比较,模型组血清ALT、AST升高,TC、TG、LDL-C升高,HLD-C降低,差异均有统计学意义(P<0.05)。与模型组比较,益生菌组、苍菊方各剂量组大鼠血清ALT、AST、TC下降(P<0.05),苍菊方中高剂量组大鼠血清大鼠血清TG下降(P<0.05),益生菌组、苍菊方中高剂量组大鼠血清HLD-C升高,苍菊方高剂量组大鼠血清LDL-C下降(P<0.05)。HE染色显示,模型组大鼠肝脏中肝细胞出现弥漫性、大小不等的空泡,出现气球样变,汇管区炎症细胞浸润明显,肝细胞排列紊乱可见大量大小脂滴,颜色深。各给药组均能改善NAFLD大鼠肝细胞内损伤程度,存在部分散在的空泡,部分肝细胞恢复正常。苍菊方各剂量组肠道菌群与模型组有不同程度的差异,逐渐接近正常组状态。结论:苍菊方能降低大鼠血清中ALT、AST、TC、TG、LDL-C水平,升高大鼠血清中HDL-C水平,并能改善NAFLD大鼠病理状态以及脂质沉积状况。其主要通过改善群落物种数目,使高脂饮食喂养的NAFLD大鼠紊乱的肠道菌群组成和结构逐渐恢复正常,从而改善NAFLD。

Reversal of idiopathic hypogonadotropic hypogonadism： a cohort study in Chinese patients

Although idiopathic hypogonadotropic hypogonadism （IHH） has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group （n = 18） and a nonreversal group （n = 336）. Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 （5.1%） acquired normal reproductive function during treatment. The median age for reversal was 24 years old （range 21-34 years）. Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone （LH） （1,0±0.7 IU 1-1 vs 0.4±0.4 IU 1-1, P 〈 0.05） and stimulated LH （28.3 ± 22.6 IU 1-1 vs 1.9 ±1.1 IU 1-1, P 〈 0.01） levels, as well as larger testicle size （5.1 ±2.6 ml vs 1.5± 0.3 ml, P〈 0.01）, at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.

Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma

Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer patients.Monoclonal antibodies targeting two such molecules,Programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4(CTLA-4)have shown clinical benefit in the treatment of advanced malignancies,including metastatic melanoma.Adverse effects of these immune checkpoint inhibitors include immune-related adverse events(irAE),of which one of the most common is autoimmune thyroiditis.Though thyroiditis is increasingly recognized,there are no reports of the pathological findings that occur in immunotherapy-induced thyroiditis.We present a case of immunotherapy-induced thyroiditis demonstrating its unique cytopathologic features.A 51-year-old woman with metastatic melanoma was found to have a suppressed TSH and elevated free thyroxine concentration 14 days after starting treatment with nivolumab(PD-1 antagonist)plus ipilimumab(CTLA-4 antagonist)therapy.A thyroid biopsy was performed based on ultrasound findings and cytopathology revealed unique features including abundant clusters of necrotic cells,lymphocytes and CD163-positive histiocytes.This case reports cytopathologic features found in immune checkpoint inhibitor related thyroiditis.These appear to be unique findings and may help inform future research regarding the pathophysiology and mechanisms of this condition.

Immune-related endocrine disorders in novel immune checkpoint inhibition therapy

Immune checkpoint inhibition against advance malignancies was named breakthrough discovery by the science magazine in 2013.In numerous clinical studies,monoclonal antibodies against the immune checkpoints,CTLA4,PD1 and PD1 ligand PDL1 have shown promising tumor response in different type of metastatic malignancies.The adverse events are autoimmune-related.The endocrine disorders,hypophysitis and thyroiditis are among the most common side effects associated with immune checkpoint inhibition treatment.Hypophysitis,a very rare endocrine disorder occurs in about one tenth of the patients receiving anti-CTLA4 treatment.Thyroiditis,on the other hand,is more commonly seen in patients receiving anti-PD1 treatment.In addition,both thyroiditis and hypophysitis are common in patients receiving combination treatment with anti-CTLA4 and anti-PD1 treatment.The time to onset of hypophysitis and thyroiditis is short.Most of the endocrine disorders occur within 12 weeks after initiation of the immune checkpoint inhibition therapy.Hypophysitis can manifest as total anterior pituitary hormone deficiency or isolated pituitary hormone deficiency.Diabetes insipidus is rare.TSH and gonadotropin deficiencies may be reversible but ACTH deficiency appears permanent.Thyroiditis can present as hypothyroidism or thyrotoxicosis followed by hypothyroidism.Hypothyroidism appears irreversible.Early identifying the onset of hypophysitis and thyroiditis and proper management of these endocrine disorders will improve the quality of the life and the outcome of this novel immunotherapy.