Intracavitary/Interstitial Applicator Plus Distal Parametrial Free Needle Interstitial Brachytherapy in Locally Advanced Cervical Cancer: A Dosimetric Study.

PURPOSE: To explore the dosimetric advantage of combining intracavitary/interstitial applicator with distal parametrial free needle interstitial brachytherapy (IC/IS+ISBT DP) based on MRI for locally advanced cervical cancer. METHODS AND MATERIALS: 77 IC/IS+ISBT DP treatment plans were developed for 34 patients with locally advanced cervical cancer from June 2016 to January 2020 in this study. We removed the free needles and devised a new IC/ISBT treatment plan based on the same principle. We then compared the dosimetric differences of D90, D98, V100, V150, V200 for HR-CTV (high-risk clinical target volume), D90 for IR-CTV (Intermediate risk-CTV) and D2cc for OARs (organs at risk) between the two groups of treatment plans for the same patient, and the paired T test was performed in parallel. Further, the dosage differences between the two group plans under different parametrial extension widths (the maximum distance of HR-CTV from the vertical direction of the uterine tandem at coronal position) were compared. The survival rate was calculated using the Kaplan-Meier method. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined by Cox regression method. RTOG/EORTC criteria were used to grade toxicities. RESULTS: A total of 297 free needles were used, with a weight ratio of 15.8% ± 0.11, and a mean insertion depth of 6.52cm ± 2.8cm. D90, D98, V100 for HR-CTV, and D90 for IR-CTV for IC/IS+ISBT DP were significantly higher than IC/ISBT for which free needles were removed (p<0.05). And the V200 for HR-CTV and D2cc for bladder, rectum and sigmoid were decreased (p<0.05). When the parametrial extension widths were greater than 3cm, the HR-CTV D90 and the D2CC for rectum, bladder and sigmoid colon for IC/IS-ISBT DP were advantageous compared to IC/ISBT (p<0.05). The 2-yr OS, PFS and local control rate (LC) were 82.3, 66.8, and 93.1%, respectively. Parametrial extension widths was the only statistically prognostic factors for PFS (p = 0.002) on univariate analysis. No grade 3 or 4 Treatment-related toxicities were observed. CONCLUSION: Our institutional experiences showed that IC/IS+ISBT DP is an effective treatment for cervical cancer patients with distal parametrial extension. IC/IS-ISBT DP had dosage advantage and clinical feasibility in locally advanced cervical cancer with distal parametrial extension when the parametrial extension widths were greater than 3cm.

Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats.

Increasing evidence indicates that stimulating hippocampal neurogenesis could provide novel avenues for the treatment of depression, and recent studies have shown that in vitro neurogenesis is enhanced by hypoxia. The aim of this study was to investigate the potential regulatory capacity of an intermittent hypobaric hypoxia (IH) regimen on hippocampal neurogenesis and its possible antidepressant-like effect. Here, we show that IH promotes the proliferation of endogenous neuroprogenitors leading to more newborn neurons in hippocampus in adult rats. Importantly, IH produces antidepressant-like effects in multiple animal models screening for antidepressant activity, including the forced swimming test, chronic mild stress paradigm, and novelty-suppressed feeding test. Hippocampal x-ray irradiation blocked both the neurogenic and behavioral effects of IH, indicating that IH likely produces antidepressant-like effects via promoting neurogenesis in adult hippocampus. Furthermore, IH stably enhanced the expression of BDNF in hippocampus; both the antidepressant-like effect and the enhancement of cell proliferation induced by IH were totally blocked by pharmacological and biological inhibition of BDNF-TrkB (tyrosine receptor kinase B) signaling, suggesting that the neurogenic and antidepressant-like effects of IH may involve BDNF signaling. These observations might contribute to both a better understanding of physiological responses to IH and to developing IH as a novel therapeutic approach for depression.

Fuzi polysaccharide-1 produces antidepressant-like effects in mice.

Current antidepressants are clinically effective only after several weeks of administration. We show that Fuzi polysaccharide-1 (FPS), a new water-soluble polysaccharide isolated from Fuzi, which has been used to treat mood disorders in traditional Chinese medicine for centuries, increases the number of newborn cells in the dentate gyrus in adult mice, and most of these cells subsequently differentiate into new neurons. We also found that FPS administration reduces immobility in the forced swim test, and latency in the novelty suppressed-feeding test. Moreover, a 14-d regimen with FPS reverses avoidance behaviour and inhibition of hippocampal neurogenesis induced by chronic defeat stress. In contrast, imipramine, a well known antidepressant, reverses this avoidance behaviour only after 4 wk of continuous administration. Finally, acute treatment with FPS had no effect on brain monoamine levels in frontal cortex but significantly increases BDNF in the hippocampus, while the antidepressant effect and enhancement of cell proliferation induced by FPS administration were totally blocked by K252a, an inhibitor of trkB in a chronic social defeat depression model, suggesting that the neurogenic and antidepressant effects of FPS may involve BDNF signalling. In conclusion, our findings suggest that FPS could be developed as a putative antidepressant with a rapid onset of action.

[Effects of Buyanghuanwu decoction on nerve proliferation in rats with sequelae of ischemic stroke].

OBJECTIVE: To examine the effect of Buyanghuanwu decoction (BYHWD) in inducing nerve proliferation in rats with sequelae of ischemic stroke. METHODS: A rat model of ischemic stroke sequelae was established by means of craniectomy in which the right common carotid artery was ligated with 4-0 silk thread followed by cauterization of the right middle cerebral artery. Programmed electric shock was administered 24 h after the onset of ischemic stroke for 2 h daily for 20 consecutive days. The rats in sham operation group were not subjected to ligation of the right common carotid artery or right middle cerebral artery occlusion. The rats in the treatment groups were given oral BYHWD for 15 consecutive days. All the rats received repeated intraperitoneal injections of the cell proliferation-specific marker 5-bromodeoxyuridine (BrdU), and the intake of BrdU in the cerebral tissues was determined by immunohistochemistry. RESULTS: The number of BrdU-immunoreactive cells in the cerebral tissues of BYHWD-treated rats was significantly greater than that in the untreated model group. CONCLUSION: BYHWD can promote nerve proliferation in rats with ischemic stroke sequelae.

[Effect of buyang huanwu decoction drug serum on expression of p53 and p21 genes in cultured rat's cerebral cortical neuron after hypoxia in vitro].

OBJECTIVE: To explore the effect of Buyang Huanwu decoction (BHD) drug serum on rat's in vitro cultured cerebral cortical neuron apoptosis induced by hypoxia, and on the expression of p53 and p21 genes in hypoxia process. METHODS: The model of hypoxia neuron apoptosis was established adopting Daniel method and treated with BHD drug serum. The neuron apoptosis rate was determined by flow cytometry with propidium iodide staining, the p53 and p21 gene expression was tested by immunohistochemical method with flow cytometry. RESULTS: BHD could significantly inhibit the neuron apoptosis induced by hypoxia and down-regulate the expressions of p53 and p21 genes. CONCLUSION: BHD shows inhibition on neuron hypoxia apoptosis and down-regulating of the p53 and p21 gene expression is one of its mechanisms.

[Effects of Buyanghuanwu decoction (BYHWT) on proliferation of cultured rat cortical neurons].

OBJECTIVE: To observe the effect of rat serum containing Buyanghuanwu decoction (BYHWT) on the proliferation of cultured rat cortical neurons, so as to understand the mechanism of BYHWT in the treatment of hypoxia brain damage. METHODS: The growth of cultured rat cortical neurons were observed by MTT assay to evaluate the effect of the serum containing BYHWT on the neurons cultured in both normal and hypoxia conditions. RESULTS: BYHWT significantly promoted proliferation of the neurons cultured under both normal and hypoxia conditions, in comparison with the response of the cells to drug-free serum (P<0.05). CONCLUSION: Some of the constituents of BYHWT in rat serum can promote the proliferation of rat cortical neurons cultured in both normal and hypoxia conditions.

[Protective effect of Buyanghuanwu Tang on cultured rat cortical neurons against hypoxiainduced apoptosis].

OBJECTIVE: To investigate the protective effect of Buyanghuanwu Tang (BYHWT), a decoction with 6 herbal ingredients, on in vitro cultured rat cortical neurons against apoptosis induced by hypoxia, and study its effect on the production of nitric oxide (NO) and oxygen free radicals and Bcl-2 expression in the neurons during hypoxia. METHODS: Models of hypoxia-induced neuron apoptosis were established and treated with sera containing BYHWT. Stained by propidium iodide, the neurons underwent apoptosis analysis using flow cytometry, and the levels of malonyl dialdehyde (MDA) and NO were measured with spectrophotometer, with Bcl-2 expression assayed by immunohistochemical method with flow cytometry. RESULTS: In BYHWT-treated neurons, apoptosis rates were significantly lower than those of the neurons subjected to hypoxia exclusively, and at the same time NO and MDA production was remarkably reduced. Bcl-2 expression, however, was up-regulated. CONCLUSION: BYHWT can protect neurons from hypoxia-induced apoptosis, the mechanism of which may lie in the elimination of NO and oxygen free radicals produced during hypoxia and up-regulation of Bcl-2 expression.