[Expert consensus on the management of adverse events of CDK4/6 inhibitors in breast cancer].

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.

[Direct intraoperative two-step distraction and reduction for basilar invagination with atlantoaxial dislocation].

Objective: To assess the clinical impact of direct two-step distraction reduction (TSDR) for basilar invagination (BI) with atlantoaxial dislocation (AAD). Methods: Retrospective analysis was conducted on the clinical data of patients who underwent TSDR and occipitocervical fusion in West China Hospital between October 2013 and March 2021. Depending on whether the preoperative decrease was greater than 50% on preoperative hyperextension X-rays, the patients were split into two groups. The neurological function [Japanese Orthopedic Association (JOA) score], atlantodens interval (ADI), the distance of odontoid process beyond McRae Line (ML) and Wackenheim Line (WL), cervicomedullary angle (CMA), O-C2 angle (OC2A), and complications incidence were compared between two groups preoperatively and postoperatively. Results: There were 12 men and 23 women among the 35 patients with BI and AAD, and the age ranged from 28 to 71 years, with an mean age of (52.0±13.4) years. In the preoperative reduction ≥50% group, there were 4 males and 9 females with an average age of (54.0±13.8) years; in the preoperative reduction <50% group, there were 8 males and 14 females with a mean age of (50.9±13.4) years. All the patients were followed-up for a mean time of (23.3±13.4) months. There was no significant difference in age, gender, bleeding, length of hospital stay and follow-up time between the two groups (all P>0.05). The JOA score, ADI, WL, ML and CMA of 35 patients were significantly improved when compared with those before operation (all P<0.05). The reduction degree of ADI, ML and WL was more than 80% in 31 cases (88.57%), 30 cases (85.71%) and 31 cases (88.57%), respectively. There was no significant difference in postoperative ADI, ML and WL between the two groups (all P>0.05). All patients had no incision infection, no loosening or breakage of the internal fixators. Dysphagia occurred in 3 patients, non-fusion happened in 1 patient, but no instability in X-ray of cervical dynamic position was found, no loosening or displacement occurred in internal fixators, and partial spontaneous fusion occurred between atlantoaxial lateral mass joints. Conclusions: For BI with AAD without atlantoaxial bony connection or serious atlantoaxial facet joint inclination, TSDR could obtain satisfactory reduction degree. The reduction degree on preoperative hyperextension X-ray doesn't affect the degree of intraoperative reduction.

[Efficacy and safety of carotid endarterectomy combined with endovascular therapy in hybrid operating room for patients with segmental atherosclerotic internal carotid artery occlusion].

The current study aimed to investigate the efficacy and safety of carotid endarterectomy combined with endovascular therapy in hybrid operating room for patients with segmental atherosclerotic internal carotid artery occlusion, and share the experience of preoperative screening of patients suitable for vascular reconstruction. A total of 20 patients with internal carotid artery occlusion (ICAO) who were admitted to the Department of Neurosurgery, General Hospital of Tianjin Medical University from May 2018 to May 2020 were collected, and 15 patients met the inclusion criteria. All patients received hybrid surgery. The total success rate of recanalization was 14/15, and only 1 patient developed ICA re-occlusion at 1 year follow up.Therefore, carotid endarterectomy combined with endovascular treatment in hybrid operating room was an alternative treatment for patients with segmental atherosclerotic internal carotid artery occlusion.

[Study on DNA methylation in HEB cells exposed to PM(2.5) by application of methylation chip technology].

Objective: To screen the differential methylation sites, genes and pathways of air pollution fine particles (PM(2.5)) on human bronchial epithelial (HBE) cells by methylation chip and bioinformation technology, so as to provide scientific basis for further study of the toxicological mechanism of PM(2.5) on HBE cells. Methods: In August 2020, HBE cells were infected with 10 µg/ml and 50 µg/ml PM(2.5) aqueous solution for 24 h, namely PM(2.5) 10 µg/ml exposure group (low dose group) and PM(2.5) 50 µg/ml exposure group (high dose group) ; uninfected HBE cells were used as control group. The DNA fragments were hybridized with the chip, the chip scanned and read the data, analyzed the data, screened the differential methylation sites, carried out GO analysis and KEGG analysis of the differential methylation sites, and analyzed the interaction relationship of the overall differential methylation sites by functional epigenetic modules (FEMs). Results: Compared with the control group, 127 differential methylation sites were screened in the low-dose group, including 89 genes, including 55 sites with increased methylation level and 72 sites with decreased methylation level. The differential methylation sites were mainly concentrated in the Body region and UTR region. Compared with the control group, 238 differential methylation sites were screened in the high-dose group, including 168 genes, of which 127 sites had increased methylation level and 111 sites had decreased methylation level. The differential heterotopic sites were mainly concentrated in the Body region and UTR region. Through FEMs analysis, 8 genes with the most interaction were screened, of which 6 genes had significant changes in methylation level. MALT1 gene related to apoptosis was found in the heterotopic site of methylation difference in low-dose group; PIK3CA and ARID1A genes related to carcinogenesis were found in the heterotopic sites of methylation difference in high-dose group; TNF genes related to tumor inhibition were found in the results of FEMs analysis. Conclusion: After PM(2.5) exposure to HBE cells, the DNA methylation level is significantly changed, and genes related to apoptosis and carcinogenesis are screened out, suggesting that the carcinogenic mutagenic effect of PM(2.5) may be related to DNA methylation.

[Relationship between triglyceride-glucose index and non-alcoholic fatty liver disease].

Objective: To explore the relationship between triglyceride-glucose index (TyG) and non-alcoholic fatty liver disease (NAFLD). Methods: 25 535 cases who participated in the health check-ups at the First Hospital of China Medical University from January 2019 to December 2019 were selected as the eligible subjects. Logistic regression analysis and receiver operating characteristic curve were used to analyze the relationship between TyG index and NAFLD risk and its diagnostic value for NAFLD. Results: NAFLD prevalence was gradually increased with the increase of the TyG index. After adjusting for other potential influencing factors, compared with the first quarter of TyG in patient with NAFLD, the OR (95%CI) in the second, third, and fourth quarter were 1.677 (1.495 ~ 1.881), 2.707 (2.397 ~ 3.057) and 4.049 (3.482 ~ 4.710), respectively. Receiver operating characteristic curve analysis showed that the best cut-off value of TyG index for the diagnosis of NAFLD was 6.9, and the area under the curve was 0.816. The sensitivity and specificity were 77.66% and 70.51%, respectively. The combined application of TyG and ALT levels had higher diagnostic value. Conclusion: TyG, as a simple and convenient biosynthetic index, is closely related to the NAFLD. In addition, when the TyG index is ≥6.9, it has a high diagnostic value for NAFLD.

[Gilbert's syndrome: hyperbilirubinemia enemy or friend].

Gilbert's syndrome is a kind of benign inherited disease of bilirubin binding disorder, mainly due to the homozygous polymorphism A(TA)7TAA in the promoter of the gene for uridine diphosphate -glucuronosyltransferase 1A1 (UGT1A1), which is a TA insertion into the promoter, designated as UGT1A1*28, with UGT activity reduction to 30% of the normal value. Therefore, circulating fat-soluble unconjugated bilirubin cannot be converted into water-soluble conjugated bilirubin, leading to unconjugated hyperbilirubinemia. Bilirubin has a strong affinity for erythrocyte phospholipids, which interferes with membrane composition and dynamics, resulting in increased erythrocytes fragility, easy rupture, and gradual shortening of survival time. However, there are no obvious sign of hemolysis or abnormal iron metabolism, erythrocytes and bone marrow morphology. A small amount of chronic hemolysis stimulates extramedullary (normal bone marrow morphology) hematopoiesis, ensuing compensatory increase in circulating erythrocytes and hemoglobin. Hyperbilirubinemia may also weaken gastrointestinal motility, increase passive diffusion and absorption across the intestinal mucosal epithelium by 1.5 to 2 times, thereby aggravating or worsening hyperbilirubinemia mainly with unconjugated bilirubin circulation, which indicates that there is a causal relationship between the circulating bilirubin concentration and rapid erythrocytes turnover and hemolysis rate in patients with Gilbert's syndrome. Interestingly, bilirubin also has significant antioxidant and anti-mutagenic activities, and the potential health benefits of mild hyperbilirubinemia in Gilbert's syndrome include reduced prevalence of cardiovascular disease, type 2 diabetes mellitus (and related risk factors), certain cancers, and cardiovascular-related and all-cause mortality. Exogenous bilirubin and biliverdin supplements in intestinal epithelial cells can be absorbed and may increase circulating concentration of these antioxidant compounds. With this information, we hope to raise awareness of the potentially harmful and beneficial effects of benign hyperbilirubinemia, and explore and develop beneficial medical interventions.

[Clinical diagnosis of alcoholic hepatitis in Tongliao City, Inner Mongolia].

Objective: To explore the current status of alcoholic hepatitis diagnosis by clinicians' in China. Methods: Clinical data of inpatients confirmed with alcohol-associated liver disease diagnosed at Tongliao Infectious Disease Hospital of Inner Mongolia from June 1, 2018 to May 31, 2019 were retrospectively analyzed. The consistency of clinical diagnosis of alcoholic hepatitis was judged according to the diagnostic criteria recommended by the National Institute of Alcohol Abuse and Alcoholism (USA), and then the alcoholic hepatitis severity assessment model recommended by international guidelines, including Maddrey discriminant function, Model for end-stage liver disease, and Glasgow alcoholic hepatitis score and ABIC scores (age, total bilirubin, international normalized ratio and creatinine) were applied to evaluate this group of cases. Results: Among 79 cases with alcohol-associated liver disease, 75 were males and 4 were females, age ranged between 27~75 (51.1±8.8) years. Alcohol consumption varied from 60 g/d to 600g/d, with an average consumption of 148.8 ± 76.6 g/d. The alcohol consumption duration ranged from 4 to 50 [average (23.9 ± 9.6)] years. According to the initial discharge diagnosis, there were 47 and 32 cases in alcoholic hepatitis and alcoholic liver cirrhosis group, respectively. The mean erythrocyte volume, serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were increased in alcoholic liver cirrhosis than alcoholic hepatitis group, while albumin and total cholesterol were lowered in alcoholic liver cirrhosis than alcoholic hepatitis group, and coagulation indexes were significantly extended. Alpha-fetoprotein of both groups were in the normal range; however, it was significantly higher in the alcoholic hepatitis group than the alcoholic cirrhosis group. The 10 cases in the alcoholic cirrhosis group met the definition and diagnosis of alcoholic hepatitis defined by the National Institute of Alcohol Abuse and Alcoholism (USA), but there was no case in the alcoholic hepatitis group. Among the 10 diagnosed cases of alcoholic hepatitis, 5, 6, 1 and 3 cases met the diagnostic criteria of Maddrey discriminant function, Model for end-stage liver disease, Glasgow alcoholic hepatitis score, and ABIC score for severe alcoholic hepatitis, respectively. The Maddrey discriminant function, ABIC score, and Glasgow alcoholic hepatitis score within the Model for end-stage liver disease scores> 20 points had 5, 1, and 3 cases, respectively. Conclusion: Alcoholic hepatitis is over-diagnosed by clinicians. Alcoholic hepatitis patients have the base of liver cirrhosis who meet the diagnostic criteria of National Institute of Alcohol Abuse and Alcoholism (USA). Patients with Model for end-stage liver disease score > 20 points have good consistency with Maddrey discriminant function score ≥ 32 points, and both can be used to evaluate the alcoholic hepatitis patient clinical severity.

Objective response of first-line chemotherapy of triple-negative breast cancer translates into survival benefit: an analysis in an independent, prospective clinical trial and a real-world setting.

This study sought to assess whether the objective response (OR, including complete response and partial response) of first-line chemotherapy can predict overall survival (OS) for patients with metastatic triple-negative breast cancer (mTNBC) in both clinical trial and a real-world setting. The survival predictable parameters were assessed in two independent cohorts, the training cohort of 236 patients as part of a phase 3 trial (CBCSG006, Trial registration number NCT0128762) and the validation cohort of 360 patients from the real-world setting. Univariable and multivariable Cox proportional hazard models were applied to explore associations with progression-free survival and OS in the training cohort and then in the validation cohort. OR (OR vs non-OR, HR, 0.438, p<0.001) together with Eastern Cooperative Oncology Group (ECOG) performance status, disease-free survival, number of metastatic organ sites and platinum-based chemotherapy used as first-line chemotherapy were observed to be independent prognostic factors for progression-free survival (PFS), and OR (OR vs non-OR, HR, 0.602, p=0.002) together with ECOG score, disease-free survival, number of metastatic organ sites and previous anthracycline and/or taxane treatment were observed to be independent predictive factors for OS in the training cohort. These predictors were confirmed in the validation cohort. For OR and non-OR group, median OS was 23.72 and 13.83 months in the training cohort (HR, 0.637, p=0.002), and 21.95 and 13.80 months in the validation cohort (HR, 0.608, p<0.001), respectively. By adding OR in the OS predictors, the concordance index (C-index) improved from 0.622 to 0.645 in the training cohort and 0.653 to 0.675 in the validation cohort. PFS and OS of mTNBC can be predicted by OR status with any regimen of first-line chemotherapy in an independent prospective clinical trial and a real-world setting. Therefore, TNBC, not like other subtypes of breast cancer, may be in need of combination chemotherapy or intense chemotherapy to achieve a high response rate for survival.

[Expert consensus on the management of adverse events of ErbB family tyrosine kinase inhibitors in breast cancer].

Human epidermal growth factor receptor-2 (HER-2) tyrosine kinase inhibitors (TKI) is the targeted drug of HER-2-positive breast cancer. Lapatinib, pyrotinib and neratinib, as ErbB family TKIs, have been approved by National Medical Products Administration and applied in the treatment of HER-2 positive breast cancer in China. The most common adverse effects (AEs) of TKI agents include diarrhea, drug-induced liver injury (DILI), nausea, vomiting, skin toxicity, cardiotoxicity and oral mucositis. The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence and characteristics of AEs of TKI, evaluated the manifestations and severity of AEs, and formulated the consensus of the management of common AEs based on the clinical experiences and updated advances from domestic and abroad studies. This consensus aims to provide the practical strategy for clinicians in the management of ErbB-family TKI-related AEs in China, and eventually enhance the patients' compliance and improve the therapeutic efficacy.

[Impact of heterotopic ossification after single-level cervical disc replacement on adjacent segment].

Objective: To investigate the impact of heterotopic ossification (HO) after cervical disc replacement (CDR) on clinical outcome and radiological outcome of adjacent segment. Methods: The data of patients underwent single-level Prestige-LP CDR between January 2008 and March 2014 in West China Hospital with a minimum 36 months of follow-up were retrospectively analyzed in this study. The incidence of HO, whether it affected clinical outcome, and its impact on adjacent segment intervertebral disc height (IDH), range of motion (ROM) and adjacent segment degeneration were observed. The data were compared with independent sample t test between the two groups. Results: Ninety-two patients were included in this study, including 48 males and 44 females, the mean age was (44±8) years, and the mean follow-up was (62±23) months. At the final follow-up, 34 patients developed HO after CDR, but the incidence of Grade 4 HO was 7.6%. In both of the HO and non-HO groups, clinical outcomes at the final follow-up were all significantly improved when compared to those before the operation. And there was no significant differences in any clinical indexes between the HO and non-HO groups. The adjacent segment IDH before operation and at the final follow-up in the HO group and non-HO group were similar(t=0.596, 0.825 and t=0.877, 0.644, all P>0.05). The preoperative adjacent segment ROM of HO group was similar with that in non-HO group(t=0.056, 0.709, both P>0.05), but the adjacent segment ROM in HO group was higher than that in the non-HO group at the final follow-up (upper adjacent segment: 10.0°±2.0° vs 9.0°±1.3°; lower adjacent segment: 10.2°±1.9° vs 8.8°±1.3°, t=2.824, 4.022, both P<0.05). The incidence of adjacent segment degeneration of HO group was higher than that of non-HO group at the final follow-up(41.2% vs 19.0%, χ(2)=5.343, P<0.05). Conclusions: HO is a common phenomenon in the long-term follow-up after the CDR operation with Prestige LP prosthesis, but HO does not affect the improvement of clinical outcome. HO after CDR might be one of important risk factors accelerating adjacent segment degeneration.

[Effects of preoperative segmental mobility on the clinical and radiographic outcomes following one-level artificial cervical disc replacement].

Objective: To investigate the effects of preoperative segmental range of motion (ROM) on clinical and radiographical outcomes after artificial cervical disc replacement (ACDR) and explore whether ACDR could be indicated for patients with preoperative limited or excessive segmental ROM. Methods: From January 2008 to December 2017, patients who underwent Prestige-LP ACDR in West China Hospital were retrospectively reviewed. The preoperative and postoperative X-rays of the cervical spine were collected to measure the radiographic parameters, including cervical lordosis (CL), C(2-7) ROM, disc height (DH), disc angle (DA) and ROM at the arthroplasty level. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) and the Neck Disability Index (NDI) scores. The correlation between preoperative segmental ROM and postoperative clinical and radiographical outcomes were also analyzed. Results: A total of 161 patients were analyzed, with 73 males and 88 females. The mean age was (44±8) years, and the follow-up period was 34 months (12-120 months). JOA and NDI scores improved after ACDR (P<0.05). However, postoperative C(2-7) ROM and ROM at the arthroplasty level were comparable with preoperative counterparts (both P>0.05). Preoperative segmental ROM positively correlated with C(2-7) ROM and ROM at the arthroplasty segment (r=0.213、0.271, both P<0.05), but was negatively correlated with the change of ROM (r=-0.534, P<0.05). The segmental ROM was 4.0°±1.0° in the limited-ROM group (A) and 14.6°±1.3° in the excessive-ROM group (B), respectively. There were significantly more patients diagnosed with cervical spondylosis in group A than in group B (35.5% vs 10.7%, P<0.05). The level-distribution was statistically different between the two groups. C(5/6) and C(6/7) were prone to limited motion in group A, while C(4/5) and C(5/6) were predisposed to excessive motion in group B (all P<0.05). After surgery, C(2-7) ROM increased for 14.2°±16.8° in group A, while paradoxically decreased for 2.2°±14.4° in group B. However, C(2-7) ROM in group B was still larger than that in group A (P<0.05). Similarly, the ROM at the arthroplasty level increased by 3.1°±3.7° in group A, whereas the values decreased by 4.4°±4.2° in group B postoperatively. In addition, group A still had less segmental ROM than group B (P<0.05). The preoperative DH in group A was less than that in group B (P<0.05). The rates of ASD, HO, and high-grade HO in group A were all higher than those in group B but without significant differences (all P>0.05). Conclusion: Preoperative segmental ROM has no significant effects on clinical outcomes after ACDR; it has a positive correlation with postoperative global and segmental ROM while is negatively correlated with ROM change.

[Diagnosis and treatment strategies for fatty liver when obesity coexists with alcohol consumption].

Non-alcoholic fatty liver disease and alcohol (ethanol)-related liver disease is a global epidemic of chronic liver disease and the main cause of fatty liver. Non-alcoholic fatty liver patients sometimes ingest different types of alcohol. Therefore, when obesity coexist with alcohol consumption, it is more difficult to diagnose the cause of fatty liver. The amount of alcohol consumption and alcohol drinking pattern and chronic liver injury, type 2 diabetes mellitus, cardiovascular disease and other metabolic-related diseases may have J-type correlation; that is to say, a light to moderate amount of alcohol consumption may bring certain benefits to the above diseases, but excessive alcohol consumption may promote the development of obesity, aggravate liver disease, metabolic abnormalities, and increase the risk of tumors. Screening for metabolic-related disease risk should be considered in addition to the assessment of changing liver lesions when obesity coexists with alcohol consumption. Changing bad living habits, losing weight and abstaining from alcohol are still the basis of treating fatty liver and metabolic disorders. Carefully selecting patients and communicating with them about the risk and benefit of drugs are important indicators of drug therapy. Patients with end-stage liver disease can be considered for liver transplantation and postoperative lifestyle improvement should be emphasized.

[Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV].

Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease （CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74 (0.34, 0.94)×109/L vs. 0.99 (0.71, 1.29)×109/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) µg/L vs. 0.11 (0.06,0.20) µg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m2 vs. 22.0 (20.0, 24.0) kg/m2，P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25.0 kg/m2, which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors （all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.

[Effect of p38MAPK gene silencing on expression of oncogenes and apoptotic genes induced by PM(2.5) in hepatocytes].

Objective: To study the effect of p38 mitogen-activated protein kinase (MAPK) gene silencing on expression of apoptotic genes and oncogenes in hepatocytes treated with PM(2.5). Methods: From June to September 2019, according to the p38MAPK gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, ligated into PLVX-shRNA2-puro after annealing, and the recombinant lentiviral vector was transfected into L02 hepatocytes. The p38MAPK silencing cells were identified by real-time fluorescent quantitative PCR and western blotting. The normal L02 cells and p38MAPK silencing cells were treated with 50 µg/mL PM(2.5) water soluble solution, 10 µmol/L positive control Cr(6+), and a blank control group was set up, the treatment time was 24 h. The mRNA levels of oncogenes (c-fos, c-myc, k-ras) , tumor suppressor gene (p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by Western blotting. Results: The expression levels of p38MAPK mRNA and protein in p38MAPK gene silencing cells were significantly lower than those in L02 hepatocytes (P<0.05) , and the p38MAPK gene silencing cell line was successfully constructed. Compared with the blank control group, the expression levels of the oncogenes c-fos, c-myc, k-ras and the apoptosis genes Caspase-3, Caspase-8 and Caspase-9 increased, the expression level of tumor suppressor gene p53 decreased in the L02 hepatocyte group treated with PM(2.5) water soluble matter, and the differences were statistically significant (P<0.05) . Compared with the L02 hepatocytes group treated with PM(2.5) water soluble matter, the expression levels of the oncogenes c-fos, c-myc, k-ras and apoptosis genes Caspase-3, Caspase-8 and Caspase-9 decreased, the expression level of tumor suppressor gene p53 increased in the p38MAPK gene silencing cells group treated with PM(2.5) water soluble matter, and the differences were statistically significant (P<0.05) . Conclusion: PM(2.5) has effects on the expression of oncogenes, tumor suppressor genes and apoptotic genes in L02 hepatocytes, while p38MAPK gene silencing can inhibit the effects of PM(2.5) on L02 hepatocytes.

[Analysis of PM(2.5) main pollutant components and sources in two cities in north and south of China].

Objective: To analyze the pollution characteristics and source of fine particulate matter (PM(2.5)) in Shenzhen and Taiyuan, two cities in the north and south of China. Methods: PM(2.5) samples were collected from the year of 2017 to 2018. The levels of 10 heavy metal elements (Pb, Al, As, etc.) , 10 water soluble ions (F(-), Cl(-), SO(4)(2-), etc.) and 16 polycyclic aromatic hydrocarbons (PAHs) (Nap, Acy, Ace, etc.) in PM(2.5) were detected by inductively coupled plasma mass spectrometry (ICP-MS) , ion Chromatography and high Performance Liquid Chromatography respectively. USA commercial carbon analysis was applied to detect organic carbon (OC) and elemental carbon (EC) . Source of PM(2.5) was analyzed by Factor analysis method. Results: The concentrations of Pb, Mn, As, Ni, F(-), OC and EC in PM(2.5) of Taiyuan city were significantly higher than those of Shenzhen City, and the concentrations of Na(+), Cl(-), and PO(4)(3-) were lower than those of Shenzhen City (P<0.05) . Except naphthalene, the concentrations of PAHs in PM(2.5) of Taiyuan city were higher than those of Shenzhen City (P<0.05) . The main sources of metal elements and water soluble ions in PM(2.5) in Shenzhen included: industry/vehicle exhaust factor (42.64%) , construction/soil factor (34.22%) and ocean factor (17.93%) . PAHs in PM(2.5) in Shenzhen mostly came from fuel oil/vehicle exhaust factor (38.58%) , coal combustion factor (30.78%) and biomass combustion factor (24.38%) . Differently, the main sources of metal elements and water soluble ions in PM(2.5) in Taiyuan included: construction factor (30.26%) , fuel oil and coal combustion factor (24.58%) , secondary particles/soil factor (22.03%) and industry factor (18.89%) . PAHs in PM(2.5) were from fuel oil/vehicle exhaust factor (54.71%) and coal combustion factor (43.54%) in Taiyuan. Conclusion: The sources of PM(2.5) pollution are different between Shenzhen and Taiyuan, the occupational health management must be continuously strengthened, measures should be strengthened contrapuntally on the basis of different pollution sources.

[Effect of c-myc gene silence on the expression of oncogenes and apoptotic genes in hepatocytes treated with PM(2).5].

Objective: To construct the c-myc gene silenced hepatocytes, study the effect of c-myc gene silence on expression of oncogenes and apoptosis genes in hepatocytes treated with PM2.5. Methods: According to the c-myc gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, the recombinant lentiviral vector was transfected into L02 hepatocytes. The real-time quantitative PCR and western blotting were used to identify the effect of c-myc gene silencing. L02 cells and c-myc gene silenced cells were used as experimental subjects. The normal L02 cells and c-myc silenced cells were treated with 50 µg/ml PM(2.5) water soluble solution, 10 µM positive control Cr(6+) and a blank control, the treatment period was 24 h. The mRNA levels of oncogenes (c-myc, c-fos, k-ras, p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by western blotting. Results: The mRNA level and protein level of c-myc decreased by 81% and 70% in c-myc silenced cells when compared with the normal L02 hepatocytes, the above results indicate that c-myc gene silenced cells were successfully constructed. After c-myc silenced cells were treated with PM2.5 water soluble solution, The mRNA levels of c-myc, c-fos, and k-ras decreased by 84.1%, 45.4%, and 54.6% (P<0.05) , p53 increased by 192.9% (P<0.05) , and the expression of Caspase-3, Caspase-8, and Caspase-9 decreased by 24.4%, 36.1%, 60.9% (P<0.05) . In the Cr(6+) positive control group, the expression of c-myc, c-fos, and k-ras decreased by 72.1%, 82.2%, and 54.0% (P<0.05) , p53 increased by 250.0% (P<0.05) , the expression of Caspase-3, Caspase-8, and Caspase-9 decreased by 34.6%, 36.0%, 68.9% (P<0.05) , respectively, when compared with the normal L02 hepatocytes (P<0.05) . Western blotting results showed that the protein levels of c-myc and c-fos increased, p53 decreased after PM(2.5) exposure; the protein levels of Caspase-3, Caspase-8, Caspase-9 increased after PM(2.5) exposure (P<0.05) . When in comparison with the c-myc silenced group, the protein levels of c-myc and c-fos decreased, p53 protein increased in PM(2).5 exposed group (P<0.05) . Conclusion: c-myc gene silenced cells were successfully constructed in this paper. PM(2.5) could promote the expression of oncogenes and apoptotic genes in L02 cells, and c-myc gene silencing can inhibit the expression of oncogenes and apoptotic genes after PM(2.5) treatment in L02 cells.

Survival after neoadjuvant chemoradiotherapy and oesophagectomy versus definitive chemoradiotherapy for patients with oesophageal squamous cell carcinoma.

BACKGROUND: Whether there is a difference in survival after neoadjuvant chemoradiotherapy plus surgery (CRT-S) compared with definitive chemoradiotherapy (dCRT) in patients with locally advanced oesophageal squamous cell carcinoma (SCC) remains controversial. METHODS: Patients with SCC who underwent curative treatment from 2008 to 2014 were identified from the Taiwan Cancer Registry. Propensity score matching was undertaken to balance pretreatment clinical variables. Overall survival was compared between patients undergoing CRT-S or dCRT. Univariable and multivariable analyses were performed to identify prognostic factors for overall survival. RESULTS: A total of 5832 patients with clinical stage II and III oesophageal SCC receiving CRT-S (1754) or dCRT (4078) were included. After propensity score matching, each group included 1661 patients. The 3-year overall survival rate for patients treated with CRT-S was 41·1 per cent compared with 17·9 per cent for those who had dCRT (P < 0·001). In multivariable analysis, treatment modality was an independent prognostic factor in the overall cohort before propensity score matching: hazard ratio 0·45 (95 per cent c.i. 0·40 to 0·51) for CRT-S versus dCRT (P < 0·001). In separate analyses of patients with clinical stage II and those with stage III disease, CRT-S was associated with significantly better overall survival than dCRT. CONCLUSION: Neoadjuvant chemoradiotherapy and oesophagectomy is associated with better overall survival than dCRT in patients with stage II and III oesophageal SCC.

[Impact of artificial disc height on the morphology of cervical facet joint].

Objective: To investigate the impact of implant height on the morphology of cervical facet joints in artificial cervical disc replacement (ACDR). Methods: A finite element model of the cervical spine from C(2) to C(7) was constructed. The surgical processes of ACDR were simulated by insertion of 5 mm, 6 mm or 7 mm Prestige-LP artificial cervical discs. The morphological changes of cervical facet joints were recorded in terms of facet overlap distance, facet overlap area and facet angle. Results: The normal height Prestige-LP cervical disc could restore the natural status of the cervical spine. Compared with the intact condition, the model with ≥2 mm height implant would reduce the overall range of motion (ROM) by 19.2% in flexion, 19.4% in extension, 18.4% in lateral bending and 19.0% in axial rotation. Besides, the ROM at the surgical level reduced by 15.8% in flexion, 15.4% in extension and lateral bending and 19.0% in rotation. The upper and lower adjacent levels (C(4/5) and C(5/6)) showed more obvious changes in ROM, which reduced by 26.8% and 26.5% in flexion, 26.6% in extension, 26.5% and 26.4% in lateral bending, and 26.4% and 26.3% in rotation, respectively. The reduction of facet overlap distance, facet angle and facet overlap area with the ≥2 mm height artifact was 9.6%, 30.7%, and 17.9% respectively at the upper adjacent level, and 22.3%, 35.3% and 28.2% respectively at the surgical level, compared with the intact model.The morphology of facet joints at the lower adjacent level were slightly changed. Conclusion: The implant height selection in ACDR should be in accordance with the physiological intervertebral disc height. Artifact with ≥2 mm in height would obviously change the morphology of facet joints, thus should not be used in clinical practice.

[Clinical study on the effects of global end-diastolic volume index-directed fluid resuscitation on the prognosis of chronic heart failure patients with septic shock].

Objective: To investigate the effect of global end-diastolic volume index (GEDI)-guided fluid resuscitation on the prognosis of patients with chronic heart failure and septic shock. Methods: This study was a prospective randomized controlled study. Consecutive eligible patients were divided into 2 groups according to the random number table method: control group (n=21) and experimental group (n=20). On the basis of routine treatment, patients in the control group received early goal-directed therapy until the central venous pressure (CVP) reaching 8-12 mmHg (1 mmHg=0.133 kPa), mean arterial pressure reaching over 65 mmHg, urine volume reaching over 0.5 ml·kg(-1)·h(-1), and central venous oxygen saturation reaching more than 70%. On the basis of routine treatment, patients in the experimental group were monitored continuously on cardiac output with pulse indication and fluid resuscitation guided by volume index GEDI. The GEDI should be maintained on the range of 680-800 ml/m(2). The remaining resuscitation goals were the same as control group. General clinical data of the two groups were collected at admission. Negative fluid balance onset time, duration of mechanical ventilation, ICU mortality and 28-day mortality were compared between the two groups. The outcomes were recorded as listed: start time of negative fluid balance, duration of mechanical ventilation, mortality in ICU and 28-day mortality. Results: There was no significant difference in age, sex, weight, APACHE Ⅱ score, SOFA score and NYHA functional class score between the two groups (all P>0.05). The negative liquid balance onset time in the control group was 3.5 (2.5, 4.0) days, which was significantly longer than that in the experimental group (2.6 (2.0, 3.0) days,U=115.0, P=0.012). The duration of mechanical ventilation was 355 (118, 552) hours in the control group, which was significantly longer than that in the experimental group (132 (36.75, 233.3) hours, U=130, P=0.038). The ICU mortality was 38.1% (8/21) in the control group, tended to be higher than that in the experimental group (20.0%(4/20), χ(2)=1.620, P=0.203). The 28-day mortality was 42.9% (9/21) in the control group, similar as in the experimental group (25.0%(5/20), χ(2)=1.482,P=0.477). Conclusion: Fluid resuscitation guided by volume index (GEDI) may improve the prognosis of patients with chronic heart failure complicated with septic shock.

[The effect of PM(2.5) on oncogene expression in HBE cells].

Objective: To study the effect of particulate matter 2.5 (PM(2.5)) on oncogene expression in human bronchial epithelial (HBE) cells. Methods: HBE cells were selected as the study subjects, and PM(2.5) treatment group (10 µg/ml and 50 µg/ml) , negative control group and positive control group (10 µmol/L Cr(6+)) were set. CCK8 assay was used to test the IC(50) value of PM(2.5). HBE cells were treated with PM(2.5) for 24 h at 10 µg/ml and 50 µg/ml, additionally, cells were treated with blank as negative control, 10 µmol/L Cr(6+) as a positive control for 24 h. After the treatment, mRNA expression of oncogenes including c-myc, c-fos, k-ras and p53 were detected by fluorescent quantitative RT-PCR, the protein expression of oncogenes were detected with western blot. Results: The IC(50) value of PM(2.5) in HBE cells is 70.12 µg/ml. The qRT-PCR data showed that compared with the control group, the expression level of c-myc gene increased by respectively 500.1%、780.7%、305.3% after exposure to 10、50 µg/ml PM(2.5) and positive control group; c-fos gene increased respectively 34.0%、76.7%、131.3% after exposure to 10、50 µg/ml PM(2.5) and positive control group; k-ras gene increased respectively 50.3%、107.0%、49.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group; p53 gene decreased by 28.3%、28.7%、59.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group. The western blot results showed that compared with the control group, c-myc protein increased respectively 29.7%、77.3% after exposure to 50 µg/ml PM(2.5) and positive control group; c-fos protein increased respectively 200.3%、137.0% after exposure to 50 µg/ml PM(2.5) and positive control group; k-ras protein increased respectively 106.3%、130.3%、116.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group; p53 protein decreased by 43.7%、53.3%、52.1% after exposure to 10、50 µg/ml PM(2.5) and positive control group. Conclusion: PM(2.5) could promote the expression of oncogenes in HBE cells, the carcinogenicity of haze might be related to promotion of oncogenes expression induced by PM(2.5).