Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics.

Background: The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods: We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results: The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion: In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC.

Efficacy and safety of radiotherapy combined with raltitrexed and irinotecan for treating unresectable recurrent colorectal cancer: a single-arm phase II trial.

Background: Local recurrence of colorectal cancer is associated with poor prognosis and quality of life. For patients not eligible for curative surgery, chemoradiation could be a promising therapeutic option, but there is no consensus yet for the concurrent chemotherapy regimen. This study evaluated the effects and safety of intensity-modulated radiation therapy (IMRT) when administered concurrently with raltitrexed and irinotecan to patients with unresectable recurrent colorectal cancer. Methods: Eligible patients developed unresectable recurrent colorectal cancer, and were refractory to, or intolerant of, chemotherapy with fluoropyrimidine and oxaliplatin. IMRT was delivered (total dose: 50-60 Gy in 25-30 fractions) concurrently with irinotecan and raltitrexed (200 and 3 mg/m2, respectively, on days 1 and 22). After treatment completion, patients underwent surgery or continued the same regimen of chemotherapy and were assessed by a multidisciplinary team. The primary endpoint was the objective response rate, defined as the proportion of patients with a confirmed complete response or partial response, assessed by radiologist and investigator after the completion of radiotherapy and reconfirmed a month later, in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1. Results: All 30 patients enrolled in this study between January 2019 and July 2020 completed radiotherapy and received a median of five chemotherapy cycles (range, 2-10 cycles). Twelve patients (40.0%) experienced an objective response (two complete responses and ten partial responses) and 17 patients exhibited stable disease [disease control rate (DCR): 96.7%]. The median follow-up was 22 months (range, 4-35 months), by the end of follow-up, six (20.0%) patients had local failure in the irradiation field, four (13.3%) had regional progression outside the irradiation field, 13 (43.3%) had distant metastasis or metastatic progression and nine (30.0%) died. The median progression-free survival (PFS) and local PFS (LPFS) were 13.5 and 23 months, respectively. The incidence of grade 3 or 4 adverse events was 26.7%, the most common of which was neutropenia (13.3%). Conclusions: IMRT with concurrent raltitrexed and irinotecan is a feasible treatment for unresectable recurrent colorectal cancer, which allows good tumor response and local control with acceptable toxicity profile.

Comparison of the efficacy and safety between a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser and a conventional Q-switched 532-nm laser for the treatment of cafe-au-lait macules in 40 Chinese children: a prospective, randomized, parallel-controlled, evaluator-blinded trial.

Cafe-au-lait macules (CALMs) affect the appearance of patients and can result in serious psychological problems. Successful treatments without adverse effects remain challenging. We designed a prospective, randomized, controlled, evaluator-blinded trial on 40 pediatric patients to compare the efficacy between a low-fluence 1064-nm Q-switched Nd:YAG laser and a Q-switched Nd:YAG 532-nm laser for the treatment of solitary CALMs in children. We randomly assigned participants into 2 groups. We treated those in the first group with 3 sessions of 532-nm QS laser at 1-month intervals, and those in the second group with 6 sessions of 1064-nm LFQS laser at 2-week intervals. We found no significant differences in treatment efficacy (p = 0.14). The 1064-nm laser group referred significantly less pain than the 532-nm laser group (p = 0.0001). Side effects were detected in 5 patients in the 532-nm laser group. The difference of the side effects was statistically significant (p = 0.04). Two patients in 532-nm laser group were recurred and none in 1064-nm laser group. On a univariate logistic regression analysis, lesions with brown color, small size, and irregular edges were significantly associated with better outcomes (> 50% clearance). Multivariate logistic regression analysis found that brown lesions and lesions with irregular edges had higher odds of getting > 50% clearance (p < 0.05). In conclusion, the 1064-nm LFQS laser produced fewer side effects, less pain, and shorter recovery time than the 532-nm laser. Irregular-bordered, smaller, brown lesions improved better than smooth-bordered, larger, light brown lesions. Moreover, the 1064-nm laser may be a better choice for treating large size CALMs. However, no significant differences were found in terms of the treatment efficacy and recurrence.

Adjuvant SOX chemotherapy versus concurrent chemoradiotherapy after D2 radical resection of locally advanced esophagogastric junction (EGJ) adenocarcinoma: study protocol for a randomized phase III trial (ARTEG).

BACKGROUND: Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. Esophagogastric junction (EGJ) adenocarcinoma, which is usually classified as gastric cancer in East Asia, often has a higher locoregional recurrence rate after operation because of its special anatomical characteristics. The aim of this study is to determine whether adjuvant radiotherapy can improve survival of locally advanced EGJ adenocarcinoma after D2 radical resection. METHODS: In this phase III, randomized, open label, controlled trial, we plan to recruit 378 patients with Siewert type II and III adenocarcinoma of EGJ, who had undergone transabdominal radical surgery and D2 lymphadenectomy, and were divided into pathological stage IIB to IIIC. All patients will be randomized 1:1 to receive either adjuvant chemotherapy alone (control group) or adjuvant chemotherapy plus chemoradiotherapy (experimental group). Patients allocated to control group will receive eight cycles of S-1 plus oxaliplatin (SOX), while the experimental group will receive two cycles of SOX followed by 45-Gy RT combined with S-1 and four additional cycles of SOX. The primary endpoint is 3-year disease-free survival rate (DFS). The secondary endpoints are 3-year overall survival rate (OS), 3-year locoregional recurrence-free survival rate (LRFS), 3-year distant metastasis-free survival rate (DMFS), and quality of life (QoL). DISCUSSION: In the past, the adjuvant treatment of EGJ adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma. In this study, EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection. TRIAL REGISTRATION: ClinicalTrials.gov NCT03973008 . Registered on 1 June 2019 (retrospectively registered), URL: https://clinicaltrials.gov/ct2/show/NCT03973008?term=NCT03973008&draw=2&rank=1.

Expanding mutational spectrum of HRAS by a patient with Schimmelpenning-Feuerstein-Mims syndrome.

As one of the epidermal nevus syndromes, Schimmelpenning-Feuerstein-Mims (SFM) is characterized by craniofacial nevus sebaceous (NS) and extracutaneous abnormalities (e.g., brain, eyes, and bone). Here, we report a case of a 4-year-old boy who presented with significant skin abnormalities (NS in the scalp, extensive epidermal nevus along Blaschko's lines), ocular abnormalities (strabismus), central nervous system abnormalities (seizure and mental retardation), lymphatic dysplasia (chylous pleural and pericardial effusion), cardiac abnormalities (patent foramen ovale), urogenital system abnormalities (cryptorchidism, hypospadias), and a tumor predisposition (embryonal rhabdomyosarcoma). DNA samples from NS, rhabdomyosarcoma, and peripheral blood leukocytes were analyzed by next-generation sequencing. A novel mutation in the HRAS gene (c.38G>T; p.Gly13Val) was detected in a mosaic state in NS, rhabdomyosarcoma, and peripheral blood leukocytes, with different ratio of heterozygous mutation (HRAS c.38G>T) of 39.90% (9412/23 588 reads), 73.03% (205 562/281 468 reads), and 14.16% (15 837/111 842 reads), respectively. By predicting the impact of the mutation on the biological function of protein, we found that the novel HRAS mutation (c.38G>T; p.Gly13Val) had the highest damaging scores among other HRAS mutations reported so far. This is the first reported SFM syndrome patient with novel mosaic HRAS mutation, which may help to expand the mutational spectrum of HRAS and better understand the role of HRAS in the disease.

miR­576­5p promotes epithelial­to­mesenchymal transition in colorectal cancer by targeting the Wnt5a­mediated Wnt/ß­catenin signaling pathway.

Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer­associated mortality. MicroRNA (miR)­576­5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR­576­5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR­576­5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR­576­5p and Wnt5a. Reverse transcription­quantitative PCR and western blotting were used to analyze the expression levels of miR­576­5p, E­cadherin, N­cadherin, vimentin, Snail1, Wnt5a, ß­catenin, c­myc, cyclin D1 and p/t­c­Jun. Using bioinformatics analysis, high expression of miR­576­5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR­576­5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial­to­mesenchymal transition (EMT). In addition, miR­576­5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/ß­catenin signaling. The results from rescue experiments further demonstrated that the effect of miR­576­5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV­939, which is an inhibitor of the Wnt/ß­catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR­576­5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a­mediated Wnt/ß­catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.

Clinical Outcomes and Safety of Different Treatment Modes for Local Recurrence of Rectal Cancer.

OBJECTIVE: Optimal approaches to patients with local recurrence of rectal cancer are unclear in China. This study aimed to evaluaty -30te the clinical outcomes and toxicity associated with different treatment regimens for patients with local recurrence of rectal cancer. METHODS: A retrospective chart review of patients with local recurrence of rectal cancer and previous radical surgical treatment between March 2010 and December 2017 with curative intent was performed. Disease-related endpoints included treatment progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 5.0, and complications were scored according to the Clavien-Dindo classification. RESULTS: A total of 71 patients met the inclusion criteria in this study. The recurrence sites were mainly local recurrence in the pelvic cavity and regional lymph node metastasis. Twenty patients received chemoradiotherapy combined with surgery, 10 underwent surgery alone, and others received chemoradiotherapy-alone (n = 27) and chemotherapy-alone (n = 14) treatment. A clear difference was found in PFS between surgery/chemoradiotherapy with surgery and chemoradiotherapy/chemotherapy groups (26.6 months vs 14.1 months, P = 0.033). The PFS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 65.2 months, 20.2 months, and 14.2 months, respectively (P = 0.042). The multivariate analysis of PFS demonstrated that surgery was an independent factor. The proportion of patients with distant metastases after chemoradiotherapy/chemotherapy was higher than that of patients undergoing surgery (36.6% vs 21.4%, P = 0.179). The OS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 89.4 months, 66.0 months, and 62.8 months, respectively (P = 0.189). Radiation treatment and surgery did not increase extra severe toxicities. CONCLUSION: Surgery combined with chemoradiotherapy was a beneficial treatment mode for managing patients with locally recurrent, nonmetastatic rectal cancer. It was associated with better local disease control, no increase in toxicity, and prolonged survival among patients with locally recurrent rectal cancer.

Identification of up-regulated transcripts during Pleurotus ostreatus primordium stage and characterization of PoALDH1.

In order to isolate the differentially expressed genes in the primordium stage of Pleurotus ostreatus, the SSH cDNA library was constructed using the cDNA from dikaryotic mycelium stage as a driver and the cDNA from primordium stage as a tester. There were 423 significantly differently expressed clones among 2055 positive clones after three times of reverse Northern blot differential screening. After the repeated sequences being removed, 46 genes were identified which were putatively involved in cell rescue and defense, energy metabolism, transcription and protein regulation, membrane proteins, and signal transduction; 18 genes encoding hypothetical proteins with unknown function; 5 genes without any homology. PoALDH1 and its full-length cDNA sequence were cloned using the Aldehyde dehydrogenase EST isolated from the library. The amino acid sequence of PoALDH1 contains conservative glutamic acid and cysteine residues active sites of aldehyde dehydrogenase family. When exposed to different concentrations of sodium chloride, the mycelium growth was inhibited and the expression level of PoALDH1 was significantly higher than that of the control one, which indicated that PoALDH1 may have the ability to relieve salt stress. The results of this study will provide useful information for isolating growth and development related genes of P. ostreatus.

miR-519b-3p promotes responsiveness to preoperative chemoradiotherapy in rectal cancer patients by targeting ARID4B.

Recent evidences demonstrate that preoperative chemoradiotherapy (pCRT) followed by mesorectal excision is an effective therapy for patients with locally advanced rectal cancer (LARC). Nevertheless, the predictive molecular biomarkers for the response of patients to CRT remain largely unknown. Here we showed that the expression of miR-519b-3p was correlated with the responsiveness to pCRT in patients with LARC. We found that miR-519b-3p was highly expressed in responsive LARC samples. And we showed that miR-519b-3p may serve as a novel predictive marker by ROC analysis. In addition, overexpression of miR-519b-3p enhanced responsiveness to chemoradiation in vitro. Mechanistically, we found that miR-519b-3p directly bond to the 3' UTR of ARID4B mRNA whose expression was inversely correlated with miR-519b-3p expression. Finally, we performed functional experiments and showed that miR-519b-3p was directly involved in response to pCRT in rectal cancer patients in an ARID4B-dependent way.

Genome-wide gene expression patterns in dikaryon of the basidiomycete fungus Pleurotus ostreatus

Abstract Dikarya is a subkingdom of fungi that includes Ascomycota and Basidiomycota. The gene expression patterns of dikaryon are poorly understood. In this study, we bred a dikaryon DK13 × 3 by mating monokaryons MK13 and MK3, which were from the basidiospores of Pleurotus ostreatus TD300. Using RNA-Seq, we obtained the transcriptomes of the three strains. We found that the total transcript numbers in the transcriptomes of the three strains were all more than ten thousand, and the expression profile in DK13 × 3 was more similar to MK13 than MK3. However, the genes involved in macromolecule utilization, cellular material synthesis, stress-resistance and signal transduction were much more up-regulated in the dikaryon than its constituent monokaryons. All possible modes of differential gene expression, when compared to constituent monokaryons, including the presence/absence variation, and additivity/nonadditivity gene expression in the dikaryon may contribute to heterosis. By sequencing the urease gene poure sequences and mRNA sequences, we identified the monoallelic expression of the poure gene in the dikaryon, and its transcript was from the parental monokaryon MK13. Furthermore, we discovered RNA editing in the poure gene mRNA of the three strains. These results suggest that the gene expression patterns in dikaryons should be similar to that of diploids during vegetative growth.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy.

BACKGROUND Increasing evidence suggests that cancer-associated inflammation is associated with poorer outcomes. The neutrophil-to-lymphocyte ratio (NLR), considered as a systemic inflammation marker, is thought to predict prognoses in colorectal cancer. In this study, we explored the association between the NLR and prognoses following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). MATERIAL AND METHODS From February 2002 to December 2012, a group of 202 patients diagnosed with LARC and receiving neoadjuvant CRT followed by radical surgery was included in our retrospective study. The associations between the pre-CRT NLR and clinicopathological characteristics, as well as the predictive value of pre-CRT NLR against survival outcomes, were analyzed. RESULTS The average NLR was 2.7±1.5 (median 2.4, range 0.6-12.8). There were 63 (31.2%) patients with NLR ≥3.0, and 139 (68.8%) patients with NLR <3.0. Correlation analyses showed that no clinicopathological characteristics except age were associated with NLR. We did not find an association between NLR and survival outcomes. In multivariate Cox model analyses, the R1/R2 resection, lymph node ratio ≥0.1, and perineural/lymphovascular invasion were independently associated with worse disease-free survival and overall survival. CONCLUSIONS In our cohort, the NLR did not correlate with survival outcomes in LARC patients undergoing neoadjuvant CRT. The prognostic value of NLR should be validated in large-scale prospective studies.

Identification of a PTPN11 hot spot mutation in a child with atypical LEOPARD syndrome.

LEOPARD syndrome (LS) is an autosomal dominant inherited disorder primarily caused by mutations in the PTPN11, RAF1 and BRAF genes. Characteristic features include lentigines, craniofacial dysmorphism, myocardium or valve abnormalities, eletrocardiographic conduction defects and deafness. LS, neurofibromatosis type 1, Noonan syndrome and Legius syndrome are a group of highly overlapped disorders termed 'RASopathies'. Therefore, clinical discrimination between these syndromes represents a huge challenge. The present study reports a young child diagnosed with LS via identification of a common p.Thr468Met mutation in PTPN11. Taking into account two Taiwanese LS cases with an identical mutation, Thr468Met is likely to be the most prevalent mutation in the Chinese population. Furthermore, this study suggests that a clinical diagnosis of LS should be considered for individuals with congenital cardiac defects and atypical lentigines (i.e., light brown freckles) scattered particularly on the face.

Downregulation of Ethylene Production Increases Mycelial Growth and Primordia Formation in the Button Culinary-Medicinal Mushroom, Agaricus bisporus (Agaricomycetes).

Ethylene biosynthesis and function in Agaricus bisporus (the button mushroom) remain uncertain. The enzyme activities of 1-aminocyclopropane-1-carboxylate (ACC) synthase (ACS) and ACC oxidase (ACO) were detectable in A. bisporus AS2796 and inhibited by α-aminooxyacetic acid and Co2+. We cloned and sequenced 2 ACS genes (Ab-ACS1 and Ab-ACS2) and 1 ACO gene (Ab-ACO) from the mushroom strain. Ab-ACS1 and Ab-ACS2 demonstrated low amino acid sequence similarity. Ab-ACO demonstrated an amino acid sequence completely identical to that of ACO1_AGABI from A. bisporus. Antisense ACO significantly reduced ACO gene expression level, ACO enzyme activity, and ethylene production in the mushroom transformants. The transformants grew faster than the wild-type strain in sterilized compost and normally formed primordia when cultivated in sterilized compost with the sterilized casing vermiculite, but the wild-type strain did not. Our results show that ethylene is synthesized in button mushrooms via the ACC pathway. Ethylene inhibited button mushroom mycelial growth and development.

Enrichment of colorectal cancer stem cells through epithelial-mesenchymal transition via CDH1 knockdown.

Cancer stem cells (CSCs) are considered to be the origin of cancer relapse and metastasis. The better understanding of CSCs, including CSCs in human colorectal cancer (CRC), may facilitate prevention and treatment. This study aimed to establish a CSC enrichment model via the induction of epithelial-mesenchymal transition (EMT) in CRC cells. We established an EMT model using the SW480 CRC cell line by CDH1 knockdown using shRNA interference. CD24+CD44+ cells were enriched in the CDH1 knockdown cells. The cells exhibited mesenchymal morphology and expressed high levels of EMT-related proteins, which confirmed that these cells had undergone EMT. Our results further showed that the proliferation rate of the transfected cells was reduced, whereas their colony-forming capacity and tumorigenesis in vivo was significantly enhanced compared to the control cells. In conclusion, these cells were highly enriched CSCs (compared to normal CSCs) and may be used as a stable model for cancer research and anticancer drug screening.

[Effect of jingui shenqi pill on morphology of injured spinal cell apoptosis in rats caused by brachytherapy].

OBJECTIVE: To study the effect of Jingui Shenqi Pill (JSP) on morphology of spinal cell apoptosis in rats injured by 192Ir irradiation. METHODS: One hundred and twenty rats were randomly divided into four groups: the model group, the JSP group, the prednisone group and the normal group. Corresponding pharmaceutics were given to rats once a day for 14 days respectively. Then except rats in the normal group, the others received 192Ir interstitial irradiation with the dosage of 22 Gy using back-fixing technology. The injured segments of spinal cord were taken out for HE staining, TUNEL examination and observation with electron microscope 8 hrs, 24 hrs and 4 weeks after irradiation. RESULTS: HE staining examination showed no obvious histological change in rats 8 and 24 hrs after irradiation, but pathological changes, as tissue rarefaction and hemorrhage did found in white matter of spinal cord shown by TUNEL 4 weeks later. Electron microscopic examination and TUNEL staining showed that as compared with the model group, the apoptotic index in the JSP and predinisone treated groups was significantly lower (P < 0.01) 8 hrs after radiation, but it showed insignificant difference between groups at the time points of 24 hrs and 4 weeks after radiation (P > 0.05). CONCLUSION: JSP could act against apoptosis of gliocyte in spinal cord of rats in early stage after brachytherapy, indicating that JSP possessing a prednisone-like action.