Evaluation of Myocardial Perfusion Classification for Interventional Treatment of Chronic Total Occlusion of Coronary Artery / 中山大学学报(医学科学版)

【Subjects】 To investigate the clinical application value of myocardial contrast echocardiography （MCE） in selecting CTO-PCI patients. MethodsFrom February 2019 to March 2020， a total of 50 patients with chronic coronary artery occlusion were consecutively selected as the research subjects. MCE and two-dimensional speck-tracking echocardiography were completed before and 12 months after interventional therapy. The primary end point was major adverse cardiovascular events. Patients were divided into groups according to the preoperative myocardial perfusion level of MCE. The improvement of left ventricular function was evaluated by two-dimensional echocardiography and left ventricular global longitudinal strain. ResultsCompared with the abnormal perfusion group， the improvement of GLS in the normal perfusion group was greater （P=0.028）. The wall motion score index （WMSI） of the abnormal perfusion group before PCI was higher than that of the normal perfusion group （P=0.002）. WMSI in the abnormal perfusion group was higher than that in the normal perfusion group one year after PCI （P<0.001）. The left ventricular GLS（P=0.008）.WMSI（P=0.016） and left ventricular end-diastolic volume（P=0.032） in the normal perfusion group were improved compared with those before operation； The postoperative perfusion score of patients with abnormal perfusion was significantly improved （ P=0.032）. ConclusionMCE has clinical application value in optimizing the selection of CTO-PCI patients. CTO patients with different myocardial perfusion types have different benefits after PCI.

Study on environmental residues detection and cleaning method of 15 cytotoxic antineoplastic drugs in PIVAS of our hospital / 中国药房

OBJECTIVE To provide a method to reduce environmental residues for pharmacy intravenous admixture service （PIVAS）， and ensure the occupational health of medical staff. METHODS The residues of 15 cytotoxic antineoplastic drugs such as gemcitabine were detected by UPLC-Q-Orbitrap-HRMS. The cleaning process was optimized with the residual quantity as the index. Nitrogen blowing method was used for alcohol volatilization experiment. CCK-8 assay was used to detect the effect of chlorine-containing disinfectant on the toxicity of cytotoxic antitumor drugs. RESULTS The linear range of 15 cytotoxic antineoplastic drugs such as gemcitabine were 0.5-1 000 ng/mL. RSDs of intra-day and intra-day precision were no higher than 20.00%. Six drugs including gemcitabine， isocyclophosphamide and cyclophosphamide were detected in the PIVAS environment of our hospital， and the residue of cyclophosphamide was relatively high. The optimal cleaning procedure was cleaning once with water + cleaning once with 1 000 mg/L chlorine-containing disinfectant + cleaning once with 75% alcohol， wiping with dry gauze method. The results of alcohol volatilization test showed that there was no significant difference in drug residues between control group and 75% alcohol group （P＞0.05）. The results of CCK-8 test showed that compared with control group， the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs were decreased significantly （P＜0.01）； the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs+chlorine-containing disinfectant were significantly higher than those treated with 15 cytotoxic antineoplastic drugs （P＜0.01）. CONCLUSIONS A method for the simultaneous determination for residues of 15 cytotoxic antineoplastic drugs such as gemcitabine in PIVAS is successfully established； the optimal cleaning procedure can significantly reduce the residues of drugs， the use of chlorine- containing disinfectant can significantly reduce the toxicity of drug， and the residual drugs will not cause secondary contamination of the operating area with alcohol volatilization.

Clinical evaluation of platelet-rich plasma in the treatment of early and middle stage knee osteoarthritis under 3.0T MRI T2 mapping sequence / 中华外科杂志

Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regeneration＆Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade Ⅲ to grade Ⅱ, one case improved from grade Ⅱ to grade Ⅰ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade Ⅰ,Ⅱ,and Ⅲ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade Ⅰ, 2.66 ms in grade Ⅱ, and 3.72 ms in grade Ⅲ).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.

Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway / 中国中药杂志

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.

A single-center retrospective analysis of 77 traumatic arterial injuries of lower extremities / 中华外科杂志

Objective: To analyze the treatment and clinical prognosis of lower extremity arterial injury caused by trauma. Methods: The clinical data of 77 patients with traumatic lower extremity arterial injury admitted to Department of Vascular Surgery,Yichang Central People's Hospital from January 2013 to June 2021 were collected retrospectively. There were 65 males and 12 females, with an average age of 47.4 years (range: 7 to 75 years). Among the 77 patients, 56 cases (72.7%) had open injury and 21 cases (27.3%) had closed injury. Iliac artery was injured in 9 cases (11.7%), common femoral artery in 7 cases (9.1%), superficial femoral artery in 1 case (1.3%), popliteal artery in 11 cases (14.3%) and inferior knee artery in 49 cases (63.6%). The treatment methods and clinical effects were analyzed. Results: One case with pelvic fracture combined the internal iliac artery injury and 1 case with multiple injuries involving the common femoral artery died of circulatory failure before surgery. Seventy-five cases received vascular-related operations, including arterial ligation in 24 cases, arterial reconstruction in 40 cases, stent graft implantation in 1 case, primary amputation in 2 cases, and arterial embolization in 8 cases. The overall mortality rate was 6.5% (5/77), all of which were closed injuries. Except for 2 cases who died before surgery, 3 cases with pelvic fracture combined the internal iliac artery injury died of multiple organ failure after internal iliac artery embolization. There were 8 cases received amputation (10.4%, 8/77), 5 cases with closed injury and 3 cases with open injury. In addition to 2 cases with primary amputation, 6 cases underwent secondary amputation due to ischemia-reperfusion injury after revascularization (4 cases with popliteal artery injury and 2 cases with subpatellar artery injury). The average followed-up time was 17 months (range: 2 months to 8 years). One patient with femoral artery injury underwent autologous great saphenous vein bypass, and lower limb artery CT angiography was re-examined 6 months after the operation, and 30% distal anastomotic stenosis was found. Ankle brachial index<0.8 was found in two patients 1 year after popliteal artery repair, but none of the patients had intermittent claudication symptoms, and no further intervention was performed. Five patients suffered delayed healing due to severe lower limb injury, fracture and skin injury. Among them, 2 cases had poor wound healing at the stump of amputation, which gradually healed 3 to 5 months after several debridements. The other 3 vascular injury combined with tibial fracture patients had delayed tibial healing after surgery, but no symptoms of vascular ischemia occurred. All the other patients recovered well and no other serious complications occurred. Conclusions: The proportion of death and disability in patients with lower limb artery injury caused by trauma is high. Active and orderly surgical repair according to the site and type of injury can reduce the mortality, save the function of the affected limb, and promote the healing of injury.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. @*Materials and Methods@#Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. @*Results@#Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). @*Conclusion@#This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. @*Materials and Methods@#Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. @*Results@#Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). @*Conclusion@#This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

The evolution of the nasopharyngeal carcinoma staging system over a 10-year period: implications for future revisions / 中华医学杂志(英文版)

BACKGROUND@#The classification criteria and staging groups for nasopharyngeal carcinoma described in the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system have been revised over time. This study assessed the proportion of patients whose staging and treatment strategy have changed due to revisions of the UICC/AJCC staging system over the past 10 years (ie, from the sixth edition to the eighth edition), to provide information for further refinement.@*METHODS@#We retrospectively reviewed 1901 patients with non-metastatic nasopharyngeal carcinoma treated in our cancer center between November 2009 and June 2012. The Akaike information criterion and Harrell concordance index were applied to evaluate the performance of the staging system.@*RESULTS@#In total, 25 (1.3%) of the 1901 patients who were staged as T2a according to the sixth edition system were downgraded to T1 in the eighth edition; 430 (22.6%) staged as N0 in the sixth edition were upgraded to N1 in the eighth edition; 106 (5.6%) staged as N1/2 in the sixth edition were upgraded to N3 in the eighth edition. In addition, 51 (2.7%) and 25 (1.3%) of the study population were upstaged from stage I to stage II and stage II to stage IVa, respectively; 10 (0.5%) was downgraded from stage II to stage I. The survival curves of adjacent N categories and staging groups defined by eighth classification system were well-separated. However, there was no significant difference in the locoregional failure-free survival (P = 0.730) and disease-free survival (P = 0.690) rates between the T2 and T3 categories in the eighth edition classification system.@*CONCLUSIONS@#Modifications to the tumor-node-metastasis staging system over the past 10 years have resulted in N classification changes in numerous cases. Although the eighth edition tumor-node-metastasis staging system better predicts survival outcomes, the T classification could be simplified in future revisions.

Analysis on the causes and prevention strategies of the vascular injury caused by the oblique lateral lumbar fusion / 中国骨伤

OBJECTIVE@#To analyze the causes of vascular injury occurred in oblique lateral interbody fusion for treating lumbar degenerative diseases, and put forward preventive measures.@*METHODS@#There were 235 patients analyzed from October 2014 to May 2017 in five hospitals, who were treated with oblique lateral interbody fusion with or without posterior pedicle screw fixation. There were 79 males and 156 females with an average age of (61.9±13.5) years old (ranged from 32 to 83 years). There were 7 cases of vascular injury, including 4 cases of segmental vessel injury, 1 case of left common iliac artery injury, 1 case of left common iliac veininjury and 1 case of ovarian vein injury.@*RESULTS@#The follow up time ranged from 6 to 36 months, averagely (15.6±7.5) months. There was no pedicle screw loosen or fracture. The low back pain VAS decreased from preoperative 6.7±2.3 to 1.4±0.8 at the latest follow-up, which was statistically difference(@*CONCLUSION@#Oblique lateral interbody fusion technique provides a new method for minimally invasive fusion of lumbar internal fixation. However, it has a risk of vascular injury. In order to effectively prevent the occurrence of vascular injury, the operative indications and careful and meticulous operation should be strictly grasped.

Polymorphism and Forensic Application of 11 Y-SNP in Guizhou Shui Ethnic Group / 法医学杂志

Objective To investigate the frequency distribution features of 11 Y-SNP of Guizhou Shui ethnic group, explore its genetic relationship with other ethnic groups and evaluate its forensic application value. Methods Multiplex amplification of the 11 Y-SNP of samples of 180 unrelated male individuals from Guizhou Shui ethnic group was performed with microsequencing technique. The frequency of haplogroup was calculated by direct counting method, and principal component analysis （PCA） of Guizhou Shui ethnic group and reference ethnic groups was performed by using Multi-variate statistical package （MVSP）. The Fst genetic distance between Guizhou Shui ethnic group and other ethnic groups was calculated with Arlequin v3.5. The phylogenetic tree was established with MEGA 4.0 software according to the Fst value. Results Six types of Y chromosome haplogroups were observed in total. Among which, the distribution frequency of O-M175 haplogroup was the highest （71.11%）, followed by C-M130 （25.00%）, and D-M174 （3.89%）. O1b-M268 （31.11%） and O2a2-IMS-JST021354 （28.33%） had a relatively high distribution frequency in O haplogroup. The paternal relationship between Guizhou Shui ethnic group and Guizhou Gelao ethnic group in the same language group was the closest. Conclusion The distribution of Y-SNP haplogroup of the Shui ethnic group in Guizhou has certain specificity, which can provide basic data for forensic biogeographic inference.

Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

The changes of the expression of 2-type small conductance-Ca- activating-K (SK2) channel protein in hypertensive rat myocardium / 中国应用生理学杂志

OBJECTIVE@#To investigate the expression of 2-type small conductance-Ca-activating-K (SK2) channel protein in hypertensive rat myocardial cells.@*METHODS@#Twelve healthy adult male SD rats were randomly divided into control group (n=5) and experimental group (n=7). The rats of experimental group were injected intraperitoneally with N'-nitro-L-arginine (L-NNA 15 mg/(kg·d))while the rats of control group were injected intraperitoneally with isometrical normal saline(15 ml/(kg·d )). The body weight, blood pressure and electrocardiogram of the rats were measured every week. After 4 weeks, the rats were sacrificed to obtain hearts, and the expression of SK2 channel protein in myocardium was detected by Western blot.@*RESULTS@#After 4 weeks of administration, compared with the control group, the blood pressure in the experimental group was significantly elevated (P＜0.05), QRS duration and R-R interval were prolonged, and the expressions of SK2 channel in the atrial and ventricular tissue of the experimental group were significantly higher than those in the control group (1.12±0.18,1.64±0.26, P ＜ 0.05).@*CONCLUSION@#The expressions of atrial and ventricular SK2 pathway are increased in hypertensive model rats. It may be one of the mechanism leading to arrhythmias in hypertensive model rats and can provide new ideas and strategies for the treatment and prognosis of hypertensive diseases.

Proposal of a Pretreatment Nomogram for Predicting Local Recurrence after Intensity-Modulated Radiation Therapy in T4 Nasopharyngeal Carcinoma: A Retrospective Review of 415 Chinese Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Local relapse-free survival (LRFS) differs widely among patients with T4 category nasopharyngeal carcinoma (NPC). We aimed to build a nomogram incorporating clinicopathological information to predict LRFS in T4 NPC after definitive intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Retrospective study of 415 Chinese patients with non-metastatic T4 NPC treated with definitive IMRT with or without chemotherapy at our cancer center between October 2009 and September 2013. The nomogram for LRFS at 3 and 5 years was generated based on multivariate Cox proportional hazards regression, and validated using bootstrap resampling, assessing discriminative performance using the concordance index (C-index) and determining calibration ability via calibration curves. RESULTS: Five-year LRFS was 88.8%. We identified and incorporated four independent prognostic factors for LRFS: ethmoid sinus invasion, primary gross tumor volume, age, and pretreatment body mass index. The C-index of the nomogram for local recurrence was 0.732 (95% confidence interval, 0.726 to 0.738), indicating excellent predictive accuracy. The calibration curve revealed excellent agreement between nomogram-predicted and observed LRFS probabilities. Risk subgroups based on total point score cutoff values enabled effective discrimination of LRFS. CONCLUSION: This pretreatment nomogram enables clinicians to accurately predict LRFS in T4 NPC after definitive IMRT, and could help to facilitate personalized patient counselling and treatment strategies.

Influence of smoking on insulin resistance in male patients with obstructive sleep apnea-hypopnea synddrome / 医学研究生学报

Objective Smoking can induce and aggravate obstructive sleep apnea-hypopnea synddrome (OSAHS), but there are few reports on its influence on insulin resistance of OSAHS patients. The article aimed to discuss the influence of smoking on insulin resistance in male patients with OSAHS.Methods A total of 141 OSAHS patients were divided into smoking group (n=104) and non-smoking group (n=37) according to smoking history. The smoking group were subdivided into two subgroups: ≥600 cigarettes/year and < 600 cigarettes/year according to smoking index. General clinical data of all patients were collected,while night sleeping data were gained by PSG overnight sleep monitoring. Fasting insulin(FINS), fasting blood glucose (FBG), concentration of serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interletkin-6 (IL-6), lipidperoxide (LPO) and activity of superoxide dismutase (SOD), glutathione peroxides (GSH-PX) were detected on all patients. Insulin resistance was evaluated by measuring HOMA-IR and FINS.Results Compared with non-smoking group, the patients in smoking group had a longer lack of oxygen time, lower oxygen saturation, higher CRP, TNF-alpha, IL-6 , LPO levels and lower SOD, GSH-PX activity. Significant differences were found in FBG, FINS, HOMA-IR and IR incidence between 2 subgroups(P<0.05), and the indexes of these 2 subgroups were both higher than those of non-smoking gorup, representing statistical significance(P<0.05).Conclusion Smoking is likely to be one of the important factors that lead to insulin resistance in male OSAHS patients. Oxidative stress, inflammation, hypoxia may be its influencing factors.

A National Study of Survival Trends and Conditional Survival in Nasopharyngeal Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology and End Results Registry / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. CONCLUSION: Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.

Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). MATERIALS AND METHODS: Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. RESULTS: Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. CONCLUSION: Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

Evaluation of A Single-reaction Method for Whole Genome Sequencing of Influenza A Virus using Next Generation Sequencing / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate a single-reaction genome amplification method, the multisegment reverse transcription-PCR (M-RTPCR), for its sensitivity to full genome sequencing of influenza A virus, and the ability to differentiate mix-subtype virus, using the next generation sequencing (NGS) platform.</p><p><b>METHODS</b>Virus genome copy was quantified and serially diluted to different titers, followed by amplification with the M-RTPCR method and sequencing on the NGS platform. Furthermore, we manually mixed two subtype viruses to different titer rate and amplified the mixed virus with the M-RTPCR protocol, followed by whole genome sequencing on the NGS platform. We also used clinical samples to test the method performance.</p><p><b>RESULTS</b>The M-RTPCR method obtained complete genome of testing virus at 125 copies/reaction and determined the virus subtype at titer of 25 copies/reaction. Moreover, the two subtypes in the mixed virus could be discriminated, even though these two virus copies differed by 200-fold using this amplification protocol. The sensitivity of this protocol we detected using virus RNA was also confirmed with clinical samples containing low-titer virus.</p><p><b>CONCLUSION</b>The M-RTPCR is a robust and sensitive amplification method for whole genome sequencing of influenza A virus using NGS platform.</p>

The Surgical Management of Traumatic Lower Cervical Spondylolisthesis with Posterior Percutaneous Pedicle Screw Fixation

We reported a technical report of traumatic lower cervical spondylolisthesisca used by bilateral pedicle fracture, without neurological compression. The patient was treated with the minimally invasive technique of percutaneous pedicle screw fixation. Fracture healing and normal cervical motion were confirmed by plain films and physical examinations on the 18-monthpostoperatively. The technique of percutaneous pedicle screw fixation might be an alternative strategy for the treatment of traumatic lower cervical spondylolisthesis with pedicle fracture.

Right ventricular outflow tract septal pacing versus apical pacing: A prospective, randomized, single-blind 5-years follow-up study of ventricular lead performance and safety / 华中科技大学学报（医学）（英德文版）

Lead placement for ventricular pacing variably impacts the physiological benefit of the patient. This study evaluated the ventricular lead performance and safety of right ventricular outflow tract septal pacing in patients with bradyarrhythmia in South China over 60-month follow-up. Totally, 192 patients (108 males, and 84 females, 63±21 years old) with bradyarrhythmia were randomly divided into two groups. The right ventricular outflow tract septum (RVOTs) group had lead placement near the septum (n=97), while the right ventricular apex (RVA) group had a traditional apical placement (n=95). RV septal lead positioning was achieved with a specialized stylet and confirmed using fluoroscopic projection. All patients were followed up for 60 months. Follow-up assessment included stimulation threshold, R-wave sensing, lead impedance and lead complications. The time of electrode implantation in both the ROVTs and RVA groups were significantly different (4.29±0.61 vs. 2.16±0.22 min; P=0.009). No differences were identified in threshold, impedance or R-wave sensing between the two groups at 1st, 12th, 36th and 60th month during the follow-up period. No occurrence of electrode displacement, increased pacing threshold or inadequate sensing was found. The long-term active fixation ventricular electrode performance in RVOTs group was similar to that in RVA group. RVOTs pacing near the septum using active fixation electrodes may provide stability during long-term follow-up period.

Mechanisms of the role of fibroblast growth factor 21 in attenuating insulin resistance / 药学学报

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on type 2 diabetic mice model and to provide mechanistic insights into its therapeutic effect. Type 2 diabetic animal model was established with high calorie fat diet and low dose streptozotocin (STZ) injection. Mice were then randomized into 5 groups: model control, FGF21 0.25 and 0.05 μmol x kg(-1) x d(-1) groups, insulin treatment group. Ten age-matched normal KM mouse administered with saline were used as normal controls. Serum glucose, insulin, lipid products and the change of serum and liver tissue inflammation factor levels between five groups of mouse were determined. The results showed that blood glucose, insulin, free fatty acids (FFAs), triglycerides, and inflammatory factor average FGF-21 of type 2 diabetes model group and normal control group were significantly higher (P < 0.01), while compared with insulin group, no difference was significant. Average blood glucose, insulin, blood lipid and inflammatory factor of FGF-21 treatment group compared with type 2 diabetes group was significantly lower (P < 0.01) and insulin group has no difference with the model control group. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF-21 significantly remits type 2 diabetic mice model's insulin resistance state and participates in the regulation of inflammatory factor levels and type 2 diabetes metabolic disorders.