Recanalization of anastomotic occlusion following rectal cancer surgery using a rendezvous endoscopic technique with transillumination:A case report

BACKGROUND Colorectal anastomotic occlusion is a serious complication of colorectal cancer surgery.Although several treatment strategies have been proposed,the mana-gement of anastomotic occlusion remains challenging.In this report,we present a case of anastomotic occlusion recanalization performed using a novel technique involving two endoscopes,one for radial incision and the other serving as a guide light.This novel technique offers significant advantages in terms of operational feasibility,reduced invasiveness,rapid recovery,and shortened hospital stay.CASE SUMMARY A 37-year-old man underwent low anterior resection and prophylactic double-lumen ileostomy for rectal cancer in June,2023.Two months later,complete anastomotic occlusion was observed on colonoscopy.Therefore,we developed a novel atresia recanalization technique.Two endoscopes were placed,one through the colonic anastomosis and the other through the anus.A radial incision was successfully made from the colonic side,guided by the light of the endoscope from the anal side.Atresia recanal-ization was performed within 20 minutes.Three weeks after recanalization,colonoscopy revealed that the diameter of the colorectal anastomosis was approximately 16 mm and the patient therefore underwent stoma reversal in September.During the follow-up period of approximately one year,the patient remained well and no stenosis or obstruction symptoms were observed.CONCLUSION Endoscopic atresia recanalization of colorectal anastomotic occlusion assisted by an opposing light source is safe and effective.

Molecular Epidemiology and Risk Factors of Carbapenem-Resistant Klebsiella Pneumoniae Bloodstream Infections in Wuhan,China

Objective:The clinical characteristics and microbiological data of patients with K.pneumoniae bloodstream infections(BSI)from January 2018 to December 2020 were retrospectively analyzed to study the molecular epidemiology of Carbapenem-resistant Klebsiella pneumoniae(CRKP).We also aimed to identify the risk factors for the development of CRKP BSI.Methods:This retrospective study was conducted at Renmin Hospital of Wuhan University from January 2018 to December 2020.The date of non-duplicate K.pneumoniae isolates isolated from blood samples was identified using the microbiology laboratory database.The data from patients diagnosed with K.pneumoniae BSI were collected and analyzed.

Safety profile of 0.0015%tafluprost eye drops in China:a post-marketing observational study

AIM:To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension(OH)in clinical practice in China.METHODS:This post-marketing observational study included patients who received tafluprost to lower intraocular pressure(IOP)within 30d between September 2017 and March 2020 in 20 hospitals in China.Adverse drug reactions(ADRs)during tafluprost treatment and within 30d after the treatment were collected.RESULTS:A total of 2544 patients were included in this study,of them 58.5%(1488/2544)had primary open angle glaucoma(POAG),21.9%(556/2544)had OH and 19.7%(500/2544)used tafluprost for other reasons.Of 359 ADRs occurred in 10.1%(258/2544)patients,and no serious adverse event occurred.The most common ADR was conjunctival hyperemia(128 ADRs in 124 patients,4.9%).Totally 1670 participants(65.6%)combined tafluprost with carbonic anhydrase inhibitors(CAIs;37.1%,620/1670),sympathomimetics(33.5%,559/1670),β-blockers(33.2%,555/1670),other prostaglandin analogs(PGAs;15.6%,260/1670)and other eye drops(15.1%,253/1670).The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs(23 ADRs in 23 patients,8.8%,23/260)and the lowest was in combination with CAIs(16 ADRs in 16 patients,2.6%,16/620).Tafluprost was applied in primary angle-closure glaucoma(41.6%,208/500),after glaucoma surgery(17.8%,89/500)and after non-glaucoma surgery(15.8%,79/500).CONCLUSION:Tafluprost is safe for POAG and OH,and tolerable when combined with other eye drops and under various clinical circumstances.

Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer

Background: Complete resection of locally advanced sigmoid colon cancer(LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemora?diotherapy(neo CRT) followed by surgery as treatment of selected patients with unresectable LASCC.Methods: We studied the patients with unresectable LASCC who received neo CRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external?beam radiotherapy to 50 Gy and capecitabine?based chemotherapy every 3 weeks. Surgery was scheduled 6–8 weeks after radiotherapy.Results: Twenty?one patients were included in this study. The median follow?up was 42 months(range, 17–57 months). All patients completed neo CRT and surgery. Resection with microscopically negative margins(R0 resection) was achieved in 20 patients(95.2%). Pathologic complete response was observed in 8 patients(38.1%). Multivisceral resection was necessary in only 7 patients(33.3%). Two patients(9.5%) experienced grade 2 postopera?tive complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0(yp M0) disease, the cumulative probability of 3?year local recurrence?free survival, disease?free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3?year overall survival was 95.2% and bladder function was well preserved.Conclusion: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate.

Effect of tankyrase 1 on autophagy in the corpus cavernosum smooth muscle cells from ageing rats with erectile dysfunction and its potential mechanism

This study compared tankyrase 1 expression and autophagy quantity between erectile dysfunction （ED） and non-ED rats＇ corpus cavernosum smooth muscle cells （CSMCs）. This study aslo explored the effect and possible mechanism of tankyrase 1 on autophagy and cell proliferation in ageing ED rats＇ CSMCs. The intracavernous pres- sure and mean systemic arterial pressure were measured to investigate erectile function so that eight 24-month-old ED and eight 8-month-old male Wistar rats were choosed respectively. The rat CSMCs were isolated and cultured by enzyme digestion, in which tankyrase 1 expression and autophagy quantity were compared. Tankyrase 1 over-expression was induced with plasmid transfection by Lipofectamine^TM. The effect of tankyrase 1 overexpression on proliferation, autophagy and mTOR pathway in 24-month-old ED rats＇ CSMCs was measured by the cell growth curve in MTT assay, cell cycle analysis in flow cytometry （FCM）, key protein expression in Western blot, autophagy quantity in transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 fluorescence. The primary CSMCs were confirmed by immunofluorescence, and the purity was 99.1% in FCM. Compared with that of 8-month-old rats, tankyrase 1 expression and autophagy quantity significantly decreased in 24-month-old ED rats＇ primary CSMCs （P 〈 0.01）. Tankyrase 1 overexpression significantly increased the growth rate （P 〈 0.05） and increased the S phase of cell cycle （P 〈 0.01）. The autophagosome quantity was remarkably increased （P 〈 0.01）, LC3-Ⅰ/Ⅱ and Beclin 1 were upregulated （P 〈 0.01 and P 〈 0.05）, and p-p70S6K （Thr389） was downregulated in 24-month-old ED rat CSMCs （P 〈 0.05）. In conclusion, Tankyrase 1 and autophagy decrease in the CSMCs from aging rats with ED, and tankyrase 1 may have a positive effect on proliferation by enhancing autophagy and regulating the mTOR signalling pathway.

Berberine Attenuates Cigarette Smoke Extract-induced Airway Inflammation in Mice:Involvement of TGF-β1/Smads Signaling Pathway

Although several studies confirmed that berberine may attenuate airway inflammation in mice with chronic obstructive pulmonary disease(COPD),its underlying mechanisms were not clear until now.We aimed to establish an experiment mouse model for COPD and to investigate the effects of berberine on airway inflammation and its possible mechanism in COPD model mice induced by cigarette smoke extract(CSE).Twenty SPF C57BL/6 mice were randomly divided into PBS control group,COPD model group,low-dose berberine group and high-dose berberine group,5 mice in each group.The neutrophils and macrophages were examined by Wright's staining.The levels of inflammatory cytokines TNF-α and IL-6 in bronchoalveolar lavage fluid(BALF)were detennined by enzyme-linked immunosorbent assay.The expression levels of TGF-β1,Smad2 and Smad3 mRNA and proteins in lung tissues were respectively detected by quantitative real-time polymerase chain reaction and Western blotting.It was found that CSE increased the number of inflammation cells in BALF,elevated lung inflammation scores,and enhanced the TGF-β1/Smads signaling activity in mice.High-dose berberine restrained the alterations in the COPD mice induced by CSE.It was concluded that high-dose berberine ameliorated CSE-induced airway inflammation in COPD mice.TGF-β1/Smads signaling pathway might be involved in the mechanism.These findings suggested a therapeutic potential of high-dose berberine on the CSE-induced airway inflammation.

Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial

Introduction: Multimodality therapy, including preoperative chemoradiotherapy(CRT) and total mesorectal excision(TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy(CCRT) involving XELOX regimen(oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.Methods: We randomly assigned patients to the TME group(TME without preoperative CCRT) or CCRT + TME group(TME with preoperative CCRT). The primary endpoint was disease-free survival(DFS); the secondary endpoints were overall survival(OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.Results: A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 %(P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 %(P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT +TME groups were 71.3 % and 70.0 %(P = 0.849), respectively. In the TME group, 16(17.0 %) patients were proven to have p TNM stage I disease after surgery. In the CCRT + TME group, 32(35.6 %) patients achieved a pathologic complete response(p CR).Conclusions: Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high p CR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorecal cancer patients with liver metastases who underwent hepatectomy.However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients.Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients.The pathologic response was evaluated according to the tumor regression grade(TRG).The prognostic role of pathologic response in recurrence-free survival(RFS) and overall survival(OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests.Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy(median RFS: 9.9 vs.6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors,and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases(all P < 0.05). A decrease in the serum carcinoembryonic antigen(CEA) level after preoperative chemotherapy predicted an increased pathologic response rate(P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens.Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

奥沙利铂和卡培他滨联合贝伐单抗加放疗的新辅助方案治疗局部晚期直肠癌:单中心Ⅱ期研究结果

背景与目的新辅助放化疗后手术被推荐为局部晚期直肠癌的标准治疗方案,可降低局部复发但对远处转移无效。所以加强系统治疗是降低远处转移风险的必要措施。本研究旨在评价奥沙利铂和卡培他滨(XELOX)联合贝伐单抗加放疗的新辅助方案治疗局部晚期直肠癌的安全性和有效性。方法Ⅱ至Ⅲ期直肠癌患者接受1个疗程的诱导化疗及XELOX加贝伐单抗的同步放化疗。放疗结束后6–8周行手术治疗,并进行3个疗程XELOX和2个疗程卡培他滨的术后化疗。本研究的主要终点是病理学完全缓解(pathologic complete response,pCR)率和安全性,次要终点为3年总生存和无进展生存。结果 2013年2月至2015年4月间招募了45例患者。所有患者均完成了新辅助治疗。7例患者(15.6%)因个人原因拒绝了后续手术治疗,其余38例患者接受了根治性切除术,括约肌保留率为84.2%,pCR率为39.5%。毒性是可接受的,分别在6例和2例患者中观察到3–4级血液学毒性和腹泻。需要手术干预的吻合口瘘的发生率为13.3%。中位随访37个月后,5例患者出现疾病进展,2例患者因癌症死亡。3年总生存率和3年无进展生存率分别为95.3%和88.6%。结论增加贝伐单抗至新辅助放化疗中获得了令人满意的pCR率和3年生存率,但也增加了吻合口瘘的风险,因此该方案不宜作为局部晚期直肠癌的常规推荐方案。

Mast Cells in Adjacent Normal Colon Mucosa rather than Those in Invasive Margin are Related to Progression of Colon Cancer

Objective: Mast cells (MC) reside in the mucosa of the digestive tract as the first line against bacteria and toxins. Clinical evidence has implied that the infiltration of mast cells in colorectal cancers is related to malignant phenotypes and a poor prognosis. This study compared the role of mast cells in adjacent normal colon mucosa and in the invasive margin during the progression of colon cancer. Methods: Specimens were obtained from 39 patients with colon adenomas and 155 patients with colon cancers treated at the Sun Yat-sen University Cancer Center between January 1999 and July 2004. The density of mast cells was scored by an immunohistochemical assay. The pattern of mast cell distribution and its relationship with clinicopathologic parameters and 5-year survival were analyzed. Results: The majority of mast cells were located in the adjacent normal colon mucosa, followed by the invasive margin and least in the cancer stroma. Mast cell count in adjacent normal colon mucosa (MCCadjacent) was associated with pathologic classification, distant metastases and hepatic metastases, although it was not a prognostic factor. In contrast, mast cell count in the invasive margin (MCCinvasive) was associated with neither the clinicopathlogic parameters nor overall survival. Conclusion: Mast cells in the adjacent normal colon mucosa were related to the progression of colon cancer, suggesting that mast cells might modulate tumor progression via a long-distance mechanism.

Enhanced Oxygen Reduction on Graphene via Y5Si3 Electride Substrate:a First-Principles Study

Manipulating the chemical reactivity of graphene toward oxygen reduced reduction(ORR)is of particular interest for both fundamental research and practical application in fuel cell.Deposing graphene on selected substrate provides a structure-intact strategy to enhance its chemical reactivity due to substrate-induced charge and interface effect.Here,we report the graphene deposited on one-dimensional electride Y5Si3 as an effective ORR catalyst in acidic media.Thermodynamic calculations suggest that depositing graphene on electride materials can facilitate the protonation of O2,which is the rate-determining step based on the four-electron reaction pathway and thus promote the ORR activity.Further electronic calculations reveal that low work function(3.5 eV),superior electrical conductivity and slight charge transfer from substrate to graphene result in the enhanced ORR performance of graphene.These findings shed light on the rational design of ORR catalysts based on graphitic materials and emphasize the critical role of substrates for energy-related electrochemical reactions.

Involvement of TRPC1 and Cyclin D1 in Human Pulmonary Artery Smooth Muscle Cells Proliferation Induced by Cigarette Smoke Extract

Cigarette smoking contributes to the development of pulmonary artery hypertension(PAH).As the basic pathological change of PAH,pulmonary vascular remodeling is considered to be related to the abnormal proliferation of pulmonary artery smooth muscle cells(PASMCs).However,the molecular mechanism underlying this process remains not exactly clear.The aim of this research was to study the molecular mechanism of PASMCs proliferation induced by smoking.Human PASMCs(HPASMCs)were divided into 6 groups:0%(control group),cigarette smoking extract(CSE)-treated groups at concentrations of 0.5%,1%,2%,5%,10%CSE respectively.HPASMCs proliferation was observed after 24 h.HPASMCs were divided into two groups:0(control group),0.5%CSE group.The mRNA and protein expression levels of transient receptor potential channel 1(TRPC1)and cyclin D1 in HPASMCs after CSE treatment were respectively detected by RT-PCR and Western blotting.The intracellular calcium ion concentration was measured by the calcium probe in each group.In the negative control group and TRPC1-siRNA transfection group,the proliferation of HPASMCs and the expression of cyclin D1 mRNA and protein were detected.Data were compared with one-way ANOVA(for multiple-group comparison)and independent t-test(for two-group comparison)followed by the least significant difference(LSD)test with the computer software SPSS 17.0.It was found that 0.5%and 1%CSE could promote the proliferation of HPASMCs(P<0.05),and the former was more effective than the latter(P<0.05),while 3%and above CSE had inhibitory effect on HPASMCs(P<0.05).The mRNA and protein expression levels of TRPC1 and cyclin D1 in 0.5%and 1%CSE groups were significantly higher than those in the control group(P<0.05),while those in 3%CSE group were significantly decreased(P<0.05).Moreover,the proliferation of HPASMCs and the expression of cyclin D1 mRNA and protein in TRPC1-siRNA transfection group were significantly reduced as compared with those in the negative control group(P<0.05).It was concluded that low concentration of CSE can promote the proliferation of HPASMCs,while high concentrations of CSE inhibit HPASMCs proliferation.These findings suggested that CSE induced proliferation of HPASMCs at least in part via TRPC1-mediated cyclin D1 expression.

First-Principles Study of Ultrathin Molybdenum Sulfides Nanowires:Electronic and Catalytic Hydrogen Evolution Properties

Molybdenum sulfides nanomaterials, such as one-dimensional (1D) nanotubes, nanoribbons, and two-dimensional (2D) nanosheets, have attracted intensive research interests for their novel electronic, optical, and catalytic properties. On the basis of first-principles calculation, here, we report a new series of 1D ultrathin molybdenum sulfides nanowires, including Mo2S6、Mo3S6 and Mo6S10 nanowires. Our results demonstrate that these ultrathin nanowires are both thermal and lattices dynamically stable, confirmed with the calculated phonon spectrum and Born-Oppenheimer molecular dynamic simulation at the temperature up to 600 K. The calculated elastic constant is 21.33, 103.22, and 163.00 eV/■ for Mo2S6, Mo3S6, and Mo6S10 nanowires, respectively. Mo2S6 and Mo3S6 nanowires are semiconductors with band gap of 1.55 and 0.46 eV, while Mo6S10 nanowires is metal, implying their potential applications in electronics and optoelectronics. In particular, ultrathin molybdenum sulfides nanowires can be used as catalysts for hydrogen evolution reaction. The calculated Gibbs free energy change for hydrogen evolution is about -0.05 eV for Mo2S6 nanowire, comparable with those of Pt and H-MoS2. The prediction of these 1D molybdenum sulfides nanowires may enrich the 1D family molybdenum sulfides and make a supplement to understand the high performance of hydrogen evolution reaction in transition-metal dichalcogenides.

Enhanced Catalytic Hydrogen Evolution Reaction in Phosphorene Nanosheet via Cobalt Intercalation

Searching alternatives to Pt-based catalyst for producing hydrogen via water splitting has gathered enormous attention to develop renewable energy. Phosphorene has been investigated widely for its large surface area, low cost, and high carrier mobility, however, the poor activity in hydrogen evolution reaction (HER) and low conductivity limit its practical application. Herein, on the basis of first-principles calculations, we demonstrate that the catalytic HER in phosphorene can be enhanced significantly with cobalt intercalations. The Co-intercalated phosphorene is metallic with charge transfer from Co atoms to phosphorene, which could enhance the catalytic activity of phosphorene. In addition, the calculated Gibbs free energy of hydrogen adsorption on Co-intercalated phosphorene bilayer is comparable to that on Pt(111) surface, independent of the degree of hydrogen coverage. Our study implies that the Co intercalation provides an effective approach to enhance the catalytic HER in phosphorene.

Myeloid sarcoma presenting as a colon polyp and harbinger of chronic myelogenous leukemia

Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue. It is known to occur more commonly in patients with acute myelogenous leukemia and less commonly in those with myelodysplastic syndrome and myeloproliferative neoplasm, such as chronic myelogenous leukemia. The most common sites of involvement include bone, skin and lymph nodes. However, rare cases have been reported in the gastrointestinal tract, genitourinary tract, or breast. Most commonly, a neoplastic extramedullary proliferation of myeloid precursors in a patient would have systemic involvement of a myeloid neoplasm, including in the bone marrow and peripheral blood. Infrequently, extramedullary disease may be the only site of involvement. It may also occur as a localized antecedent to more generalized disease or as a site of recurrence. Herein, we present the first case in the English literature of a patient presenting with an isolated site of myeloid sarcoma arising in the form of a colonic polyp which, after subsequent bone marrow biopsy, was found to be a harbinger of chronic myelogenous leukemia.

High-Performance Chemical Information Database towards Accelerating Discovery of Metal-Organic Frameworks for Gas Adsorption with Machine Learning

Chemical structure searching based on databases and machine learning has at-tracted great attention recently for fast screening materials with target func-tionalities.To this end,we estab-lished a high-performance chemical struc-ture database based on MYSQL engines,named MYDB.More than 160000 metal-organic frameworks(MOFs)have been collected and stored by using new retrieval algorithms for effcient searching and recom-mendation.The evaluations results show that MYDB could realize fast and effcient key-word searching against millions of records and provide real-time recommendations for similar structures.Combining machine learning method and materials database,we developed an adsorption model to determine the adsorption capacitor of metal-organic frameworks to-ward argon and hydrogen under certain conditions.We expect that MYDB together with the developed machine learning techniques could support large-scale,low-cost,and highly convenient structural research towards accelerating discovery of materials with target func-tionalities in the eld of computational materials research.

Effects of different hypoxia time on hematology and histomorphology of rats at 7 000 m altitude

Objective:To observe the effects of different hypoxia time on hematology and histomorphology of rats by simulating the environment of 7000m altitude,and to provide the basis for the establishment of acute hypoxia model.Methods:40 SD rats were randomly divided into 0h hypoxia group,6h,12h,24h,and 36h group.The hypoxia environment at 7000m was simulated by low-pressure oxygen chamber.The serum SOD,MDA,LDH biochemical indexes and the morphological changes of HE staining in heart,lung and brain tissues of rats were detected under different hypoxia time.Results:Compared with hypoxia group for 0h,the number of RBC in acute hypoxia group for 6h decreased and increased with the prolongation of hypoxia time,and the highest number of RBC.The WBC,LYMP,GRAN,HGB,HCT and RCT counts of the acute hypoxia group decreased for 6h,and the above indexes increased with the prolongation of hypoxia time.Compared with the 0h hypoxia group,SOD activity in serum decreased at different hypoxia time,and MDA content in the 24h and 36h hypoxia groups showed a fluctuating change and reached a peak at 12h hypoxia.The activity of LDH fluctuated,and reached the peak at 12hLDH after hypoxia,and then gradually decreased.He staining of the brain tissue of the heart and lung,which was close to normal after hypoxia for 36h,showed that with the prolongation of the hypoxia time,the damage degree of each organ increased continuously.Interstitial pneumonia or perivasculitis occurred in the lung,and perivascular edema and pulmonary interstitial widening were observed.Cardiac tissue showed obvious degeneration and necrosis of cardiomyocytes,lysis and necrosis of local myocardial interstitium and valve fibers.A large number of inflammatory cells could be seen infiltrating into the brain tissue in the CA2 CA3 DG region.The neuron cells were denatuated,the cell volume was reduced,basophilic was enhanced,and the nerve cells were triangular.The cells were pyknotic and basophilic,with a few transverse axis structures.Conclusion:acute low pressure hypoxia can cause red blood cells white blood cells within 6 h number of platelets Hemoglobin concentrations were lower,as after hypoxia prolonged period of count increased serum biochemical index SOD activity were lower,the content of MDA and activity of LDH outer-plane changes Can cause heart lung tissue pathological damage,and increased with prolonged.

Neoadjuvant oxaliplatin and capecitabine combined with bevacizumab plus radiotherapy for locally advanced rectal cancer: results of a single-institute phase II study

Background:Neoadjuvant chemoradiotherapy followed by surgery is recommended as the standard of care for locally advanced rectal cancer,reducing local recurrence but not distant metastasis.Intensified systemic therapy is warranted to reduce the risk of distant metastasis.The present study aimed to evaluate the safety and efficacy of neo-adjuvant oxaliplatin and capecitabine(XELOX)combined with bevacizumab plus radiotherapy for locally advanced rectal cancer.Methods:Patients with stages II to III rectal cancer received one cycle of induction chemotherapy and concurrent chemoradiotherapy with XELOX plus bevacizumab.Surgery was performed 6-8 weeks after completion of radiotherapy,and postoperative chemotherapy with three cycles of XELOX and two cycles of capecitabine were given.The primary endpoints were pathologic complete response(pCR)rate and safety,and the secondary endpoints were 3-year overall survival and progression-free survival.Results:Forty-five patients were enrolled between February 2013 and April 2015.All completed the neoadjuvant therapy.Seven patients(15.6%)refused subsequent surgical therapy for personal reasons,and the other 38 patients received radical resection,with a sphincter preservation rate of 84.2%and a pCR rate of 39.5%.Toxicity was acceptable,with grades 3-4 hematological toxicity and diarrhea observed in six and two patients,respectively.Incidence of anastomotic leak that required surgical intervention was 13.3%.After a median follow-up period of 37 months,five patients developed disease progression and two died of cancer.The 3-year overall survival rate and 3-year progres-sion-free survival rate were 95.3%and 88.6%,respectively.Conclusions:The addition of bevacizumab to neoadjuvant chemoradiotherapy resulted in a satisfying pCR rate and 3-year survival,but also may increase the risk of anastomotic leak,thus this regimen is not suitable to be considered for regular recommendation for locally advanced rectal cancer.

Reprogramming immunosuppressive myeloid cells by activated T cells promotes the response to anti-PD-1 therapy in colorectal cancer

Overcoming local immunosuppression is critical for immunotherapy to produce robust anti-tumor responses.Myeloid-derived suppressor cells(MDSCS)are key regulators of immunosuppressive networks and promote tumor progression.However,it remains unclear whether and how tumor-infltrating MDSCS are shaped in response to anti-PD-1 treatment and what their impact on therapeutic efficacy is in colorectal cancer(CRC).In this study,the levels of infltrating MDSCS were significantly higher in the non-responding organoids and were selectively reduced in the responding group,with MDSCS showing increased apoptosis and attenuated functional activity after anti-PD-1 treatment.A negative correlation between T-cell activation and MDSC function was also observed in fresh human CRC tissues.Mechanistic studies revealed that autocrine IFN-α/B upregulated TRAIL expression on activated T cells to elicit MDSC apoptosis via the TRAIL-DR5 interaction and acted synergistically with TNF-α to inhibit MDSC function of suppressing the T-cell response through the JNK NMDAR-ARG-1 pathway.Moreover,blockade of IFNa/βand TNF-α abolished the therapeutic efficacy of anti-PD-1 treatment by preserving the frequency and suppressive activity of infltrating MDSCS in a CRC mouse model.This result suggested that reprogramming MDSCS by IFN-α/βand TNF-α from activated T cells was necessary for succesful anti-PD-1 treatment and might serve as a novel strategy to improve the response and efficacy of anticancer therapy.