Interventional radiotherapy, also known as brachytherapy, is the use of sealed radioactive sources that directly deliver radiation to the tumor or tumor bed. Its unique dose distribution profile allows for high conformality, making it a very useful modality in the treatment of cancers in the head and neck, where different organs and substructures that serve various but related functions are situated close to each other. In recent years, we have seen several important technological breakthroughs in the field, especially regarding its application in head and neck cancers. These include advances in treatment delivery, dosimetry planning , image guidance , and catheter positioning techniques . These innovations, which often require interdisciplinary interventions, have resulted in enhanced treatment accuracy, and therefore, major clinical advantages in terms of increased local control and decreased toxicity, as well as economic benefits. In order to highlight the differences from old brachytherapy techniques, a more appropriate terminology should perhaps be adopted, to signify these advancements that resulted in new opportunities, approaches and better outcomes – interventional radiotherapy (IRT). Such a change in terminology will not only allow recognition of these advances, but also a meaningful distinction from obsolete techniques and suboptimal outcomes that are associated with traditional brachytherapy. This is very important in increasing awareness among professionals outside the field of radiation oncology. We briefly review these recent advances, the current indications, and future directions for IRT in head-and-neck cancers.
Brachytherapy

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

OBJECTIVE Cannabinoids modulate do-pamine(DA)transmission and DA-related behavior,which has been thought to be mediated initially by acti-vation of cannabinoid CB1 receptors(CB1Rs)on GABA neurons.However,the cellular and receptor mechanisms underlying cannabinoids' psychoactive effects are not fully understood.The present study is to explore the pos-sible expression character of CB1Rs and elucidated the underlying mechanism of them.METHODS We took advantage of RNAscope in situ hybridization(ISH)assays and triple-staining assays to detect the CB1R-expressing neurons.We established an optical intracranial self-stimulation(OICSS)behavioral model by using opto-genetics to study dopaminergic reinforcement function.Natural and synthetic cannabinoids were used to study the function of CB1Rs.Conditional genetic depletion of CB1Rs and behavioral assay were performed to study the modulatory role of CB1Rs in DA-related behaviors.RESULTS We found that CB1Rs are also expressed in a subset of DA neurons and functionally underlie cannabi-noid action in male and female mice.ISH assays demon-strated CB1 mRNA in tyrosine hydroxylase(TH)-posi-tive DA neurons in the ventral tegmental area(VTA)and glutamate decarboxylase 1(GAD1)-positive GABA neu-rons.The CB1R expressing DA neurons were located mainly in the middle portion of the VTA with the number of CB1-TH colocalization progressively decreasing from the medial to the lateral VTA.Triple-staining assays indi-cated CB1R mRNA colocalization with both TH and vesicular glutamate transporter 2(VgluT2,a glutamate neuronal marker)in the medial VTA close to the midline of the brain.Optogenetic activation of this population of DA neurons was rewarding as assessed by OICSS.D9-tetrahydrocannabinol(D9-THC)or ACEA(a selective CB1R agonist)dose-dependently inhibited optical intra-cranial self-stimulation in DAT-Cre control mice,but not in conditional knockout mice with the CB1R gene absent in DA neurons.In addition,deletion of CB1Rs from DA neurons attenuated D9-THC-induced reduction in DA release in the NAc,locomotion,and anxiety.CONCLU-SION Our results indicated that CB1Rs are expressed in a subset of DA neurons that corelease DA and gluta-mate,and functionally underlie cannabinoid modulation of DA release and DA-related behavior.

OBJECTIVE：To investigate the effects of d exmedetomidine on postoperative delirium （POD） in liver tumor resection elderly patients with sleep disorder （SD）. METHODS ：Totally 80 patients undergoing liver tumor resection with preoperative Pittsburgh sleep quality index （PSQI）score ≥7 were selected from the Affiliated Cancer Hospital of Zhengzhou University from Jan. 1st，2020 to Oct. 31st，2020. They were randomly divided into group SD and group Dex according random number table ，with 40 cases in each group. At the same time ，40 patients with preoperative PSQI score ＜7 were selected as group C. Thirty min before anesthesia induction ，Dexmedetomidine hydrochloride injection 0.4 μg/kg was injected intravenously in group Dex. Etomidate emulsion injection ，Sufentanil citrate injection and Rocuronium bromide injection were used for anesthesia induction in 3 groups，and Ropofol medium/long chain fat emulsion injection + Remifentanil hydrochloride for injection was used to maintain anesthesia. The drug use ，operation time ，PACU stay time and postoperative hospital stay were recorded in 3 groups. The cognitive function was evaluated 2 h before operation and 1，3，5，7 days after operation. The occurrence of POD was observed. The plasma levels of IL- 6 and S 100β were measured 2 h before operation ，2 h after operation ，1，3，5 days after operation. The occurrence of ADR was recorded. RESULTS ：There was no statisti cal significance in intraoperativ e drug use and operation time among 3 groups （P＞0.05）. The PACU stay time ， the incidence of POD and the duration of POD in group SD an d lixxi18@126.com group Dex were significantly higher or longer than group C ， while the Dex group was significantly lower or shorter thangroup SD （P＜0.05）. The postoperative hospitalization stay ofgroup SD was significantly longer than group C and group Dex （P＜0.05），and there was no statistical significance between group Dex and group C （P＞0.05）. Before operation ，there was no statistical significance in MMSE scores or plasma levels of IL- 6 and S100β among 3 groups（P＞0.05）. MMSE scores of group C 1，3 days after operation ，those of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than those before operation. MMSE scores of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than group C at corresponding period ；the group Dex was significantly higher than the group SD at corresponding period （P＜0.05）. The plasma levels of IL- 6 and S 100 β at different time points were significantly higher than before operation ，and the group SD and group Dex were significantly higher than the group C ，and the group Dex was significantly lower than group SD at corresponding period （P＜0.05）. There was no statistical significance in the total incidence of ADR among 3 groups（P＞0.05）. CONCLUSIONS ：SD can promote the occurrence of POD in liver tumor resection elderly patients. Dexmetomidine can reduce the incidence of POD in elderly patients with preoperative SD ，the mechanism of which may be associated with the inhibition of IL- 6 and S 100β expression and the alleviation of brain injury with good safety.

Objective: Yingying, Email: yywdentist@163.com, Tel: 86⁃28⁃85503579 【Abstract】 Objective To explore the effect of 1,25(OH) 2 D 3 on the regulation of bone metabolism in a high⁃glucose environment and to provide evidence for the possible regulatory mechanism of 1,25(OH) 2 D 3 on osteoblasts in a high⁃glu⁃ cose environment. Methods: The osteoblast cell line MC3T3⁃E1 was cultured in 3 groups: ① control group, cultured in low⁃glucose (5.5 mmol/L) DMEM; ② high⁃glucose group: cultured in high⁃glucose (22 mmol/L) DMEM; ③ high⁃glu⁃ cose +1,25(OH) 2 D 3 group: high⁃glucose DMEM + 1,25(OH) 2 D 3 medium culture. The CCK⁃8 method was used to detect cell proliferation in each group; Annexin V and FITC apoptosis kits were used to detect apoptosis; Alizarin red was used to semiquantitatively analyze cell differentiation; qRT⁃PCR was used to detect forkhead transcription factor⁃1 (forkhead transcription factor 1, FoxO1) mRNA expression. Immunofluorescence was used to observe the changes in FoxO1 pro⁃ tein expression and its relative position in the nucleus. Results: ence was used to observe the changes in FoxO1 pro⁃ tein expression and its relative position in the nucleus. Results Our analysis showed that compared with those in the control group, the osteoblast apoptosis and proliferation in the high⁃glucose group were improved, while differentiation was inhibited (P < 0.05); at the same time, the mRNA expression of FoxO1(P = 0.006) was reduced. The immunofluores⁃ cence results showed that more FoxO1 was inside the nucleus (P < 0.001). Compared with those in the high⁃glucose group, excessive proliferation was inhibited, apoptosis was reduced, and osteogenic differentiation was improved in the high⁃glucose +1,25(OH) 2 D 3 group (P < 0.05); furthermore, FoxO1 mRNA was decreased (P = 0.006), and the transfer of FoxO1 protein was blocked (P < 0.001). Conclusion re, FoxO1 mRNA was decreased (P = 0.006), and the transfer of FoxO1 protein was blocked (P < 0.001). Conclusion We found that 1,25(OH) 2 D 3 may prevent the transfer of FoxO1 to the cell nucleus, inhibit the abnormal proliferation and apoptosis of osteoblasts in a high⁃glucose environment, and re⁃ verse the inhibitory effect of high glucose on the differentiation of osteoblasts.

Iron deficiency anemia is the most frequently experienced anemia in common daily practice. It is often difficult to treat due to gastrointestinal side effects of iron drugs. We report a difficult case of iron-deficiency anemia with intolerance to oral iron supplementation, which was resolved by concomitant use of Kampo. Thirty-five-year-old woman visited us because of menoxenia continuing since she was 17 years old. Although tokishakuyakusan with kakobushimatsu (processed aconite root powder) had been administered, remarkable anemia such a low hemoglobin (Hb) level (7.8 g/dL) was observed. After we added an oral iron agent for 5 months, the hemoglobin level increased to 12.8 g/dL, and epigastric discomfort appeared. Therefore, we discontinued iron agent and switched to Kampo monotherapy, but anemia gradually worsened again. Following intravenous iron infusions could not improve the iron deficiency state. Then we administered ryokeijutsukanto with kojinmatsu (ginseng powder) and lower dose of oral iron agent than before, with reference to sinshato described in “Sokeitei Ijishogen” written by Nan'yo Hara. After administration, Hb and serum ferritin level improved from 11.6 g/dL and 4.0 ng/mL to 12.3 g/dL and 32.0 ng/mL, respectively. After that, the iron metabolism marker kept stable, although the oral iron agent had been further reduced. The main indications of sinshato are palpitation, shortness of breath, dizziness and edema according to the original text. These symptoms can be interpreted as ones related to anemia. In our case, it was suggested that prescription composition of sinshato promoted iron absorption and improved anemia.

We report a case of salvage lymphadenectomy for an isolated metastatic lesion in the para-aortic lymph node (LN) in a 49-year old woman with a history of cervical cancer, initially treated with radical hysterectomy and adjuvant radiotherapy. Preoperative 3-dimensional (3D) computed tomography (CT) angiography clearly revealed a huge retro-crural metastatic LN with distinct demarcation. A metastatic lesion, more than 10 cm in size, was located behind the vena cava, aorta, and left kidney, encompassing the left renal and lumbar arteries. The metastatic LN was excised along with the left kidney. On histologic examination, the tumor was found to have invaded the pelvis of the left kidney. Compared with conventional imaging techniques, 3D CT angiography can more clearly visualize such lesions. Thus, 3D CT angiography provides useful anatomical information, such as the exact size and location, and provides clear visualization and demarcation.
Angiography* ; Aorta ; Arteries ; Female ; Humans ; Hysterectomy ; Kidney ; Lymph Node Excision* ; Lymph Nodes ; Pelvis ; Radiotherapy, Adjuvant ; Recurrence ; Uterine Cervical Neoplasms*