Clinically,pancreatic cancer is a highly aggressive tumor,and neurotropic growth is an important biological feature of pancreatic cancer.Nerve invasion brings great pain burden to patients,and it seriously affects the quality of life and the will to survive of patients.The"three-step analgesia principle"for the management of cancer pain proposed by World Health Organization(WHO)is a traditional therapeutic regimen for cancer pain.However,because of its obvious toxic side effects,poor efficacy,easy addiction,easy drug resistance,non-standard medication of clinical physicians,etc.,the"three-step analgesia principle"is unable to meet the needs of the patient's condition..In recent years,with the development of interventional technology and the development of extensive clinical trials,the interventional means,which is regarded as the"fourth step"of cancer pain management,has achieved great clinical effect,it includes various therapeutic methods and imaging-guided techniques such as neural destruction(denervation),125I particle implantation,patient-controlled analgesic pump technology,implantation of intrathecal drug infusion system,etc.,and clinical practice has proved that these techniques have significant clinical efficacy and they can provide a convenient,safe and effective treatment method for HCC patients.

Objective:To establish a disk (CD) microfluidic chip detection platform for the rapid detection of CALR-1 and CALR-2 mutations in patients with cerebral infarction, and summarize its clinical application value.Methods:Based on microfluidic technology and loop mediated isothermal amplification technology, a CD microfluidic chip detection platform for simultaneous detection of CALR-1 and CALR-2 gene mutations were established, and the sensitivity, specificity, repeatability and accuracy of the platform were verified. A total of 124 patients with cerebral infarction treated in Huashan Hospital, Shanghai Medical College, Fudan University from November 2019 to March 2021 were prospectively selected into the experimental group; and 80 healthy subjects were included in the control group. The CALR-1 and CALR-2 gene mutations in anticoagulant peripheral blood samples were detected by the CD microfluidic chip. Each chip could detect 4 samples at the same time and synchronously detect 3 indexes of each sample. The detection results could be obtained after isothermal amplification for 40 min. At the same time, sequencing method was used to verify the test results, and the consistency of the results of the two detection methods was compared.Results:Using this CD microfluidic chip platform, the synchronous amplification of 3 indexes in the sample could be completed within 40 min without the need of thermal circulation, and the whole detection process of the sample could be completed within 60 min. For samples with a high concentration of target nucleic acid, typical positive signals could be visualized after amplification for 10 min, and the test results would be available within 30 minutes after receiving the samples. The detection sensitivity of CD microfluidic chip method for CALR-1 and CALR-2 mutation load concentration was 1.0% and 0.5% respectively. Nonspecific amplification was not observed for the non-target nucleic acid samples, indicating the high specificity of this method. The coincidence rates of intra and inter batch repeatability were 100% (20/20) respectively. Two samples with CALR gene mutation were found in the cerebral infarction group, both of which were CALR-1 mutations (L367fs*46). There was no CALR-1 or CALR-2 mutation in the control group. The detection results of CD microfluidic chip method were completely consistent with the sequencing verification results (100% [204/204]).Conclusions:The CD microfluidic chip method could be used for the detection of CALR-1 and CALR-2 gene mutations in clinical samples of patients with cerebral infarction. This method has the advantages of high detection sensitivity, good detection specificity, fast detection speed and high detection flux, which is helpful to clarify the etiology of patients with cerebral infarction.

ObjectiveTo investigate the effect of the expression of HBcAg in hepatocytes on the serum level of HBcAb and seroconversion of HBeAg after antiviral therapy with nucleos(t)ide analogues (NUCs). MethodsSerum samples and liver tissue paraffin sections were collected from 101 chronic hepatitis B (CHB) patients who received antiviral therapy with NUCs in Nanfang Hospital and Panyu Central Hospital from January 2015 to June 2018. ELISA was used to measure the serum level of HBcAb, and immunohistochemistry was used to measure the expression of HBcAg in the liver. The GEO database (GSE96851) was analyzed to obtain differentially expressed genes in the liver of patients with HBcAg-positive hepatitis. The two-independent-samples t test was used for comparison of continuous data between two groups; the multiple-independent-samples nonparametric Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and Dunnett method was used for further comparisons; the chi-square test was used for comparison of categorical data between groups. ResultsThe expression pattern of HBcAg in hepatocytes was classified as absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression, and according to expression level, HBcAg expression was classified as grades Ⅰ, Ⅱ, Ⅲ, and Ⅳ expression. HBeAg seroconversion rates after 96 weeks of antiviral therapy were 5.88%, 16.67%, 22.73%, and 24.24%, respectively, in the patients with absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression (χ2=4753, P=0.037), and HBeAg seroconversion rates after 96 weeks of antiviral therapy were 5.88%, 13.04%, 27.59%, and 26.67%, respectively, in the patients with grade Ⅰ, Ⅱ, Ⅲ, and Ⅳ expression (χ2=6.580, P=0.016). There were significant differences in the serum levels of HBcAb-IgM and total HBcAb between the patients with absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression of HBcAg (HBcAb-IgM: H=9.760, P=0.021; total HBcAb: H=21.46, P＜0.001), and there were also significant differences in the serum levels of HBcAb-IgM and total HBcAb between the patients with grade Ⅰ, Ⅱ, Ⅲ, and IV expression of HBcAg (HBcAb-IgM: H=18.80, P＜0.001; total HBcAb: H=26.03, P＜0.001). The analysis of differentially expressed genes in the liver showed that the expression of antibody-related genes was upregulated in the liver of patients with HBcAg-positive acute liver failure. ConclusionThe expression pattern and level of HBcAg in the cytoplasm of hepatocytes are associated with serum HBcAb, and the measurement of HBcAg may help to predict the efficacy of antiviral therapy with NUCs.

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.
Aged ; Betacoronavirus ; isolation & purification ; Cannula ; Coronavirus Infections ; therapy ; Humans ; Oxygen ; administration & dosage ; Pandemics ; Pneumonia, Viral ; therapy

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 infection. Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial flow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.
Aged ; Betacoronavirus ; Cannula ; Coronavirus Infections ; complications ; therapy ; Humans ; Hypoxia ; etiology ; prevention & control ; therapy ; Masks ; Oxygen ; administration & dosage ; Oxygen Inhalation Therapy ; instrumentation ; standards ; Pandemics ; Pneumonia, Viral ; complications ; therapy

Objective To evaluate FIB-NLR,a combined neutrophil-lymphocyte ratio (NLR) and fibrinogen concentration (FIB) in predicting the prognosis of gastrointestinal stromal tumors (GIST).Methods Data of 79 GIST patients who underwent surgery from Jun 2010 to Dec 2014 were retrospectively analyzed.Patients were divided into 3 groups:NLR ＜ 2.30 and FIB ＜ 3.85 g/L were defined as group 0,NLR≥2.30 and FIB ＜3.85 g/L or NLR ＜2.30 and FIB≥3.85 g/L as group 1,NLR≥2.30 and FIB≥3.85 g/L as group 2.The clinicopathological features of the three groups and the 5-year recurrence-free survival rate after surgery were compared.Results FIB concentration and NLR were significantly correlated with NIH risk grade and tumor size in GIST patients (x2 =9.517,12.41 1,6.081,20.067,all P ＜ 0.05).FIB-NLR was closely related to tumor size,tumor risk and tumor mitosis (x2 =14.406,12.514,28.225,all P ＜ 0.05).Survival analysis showed that high FIB predicts lower 5-year recurrence-free survival rate,it was 87.4％ for group 0,60.8％ for group 1,21.1％ for group2,x2 =29.617,P＜0.000).Conclusion FIB-NLR independently predicts the prognosis of gastrointestinal stromal tumors.

Objective To investigate the regulation of interferon α-1b (IFNα-1b) on protein kinase Cε(PKCε) and protein kinase Cα(PKCα) which inhibit the fibrosis of hepatic stellate cells (HSC) ,and to explore its mechanism .Methods HSC-T6 cells were treated with different levels of IFNα-1b (100 , 200 ,400 ,800 and 1000 U/mL) and the proliferation of HSC-T6 cells was analyzed by methyl thiazol tetrazolium (MTT) assay .Changes of hydroxyproline level were analyzed .The expressions of PKCεand PKCαwere detected by immunofluorescence staining . PKCε, PKCα,β-catenin and Survivin mRNA levels were detected by RT-PCR . PKCε, PKCα,β-catenin and Survivin protein levels were detected by Western blot . Variance analysis was conducted by using one-way ANOVA approach . Results The inhibition rates of 100 , 200 , 400 , 800 and 1000 U/mL IFNα-1b treatment after 24 hours of administration were (15 .85 ± 1 .05)％ ,(36 .59 ± 1 .03)％ ,(45 .12 ± 1 .05)％ ,(50 .00 ± 1 .01)％ and (62 .20 ± 1 .02)％ ,respectively ,with statistically significant differences among groups (F=27 .478 , P<0 .01) .The 48h inhibition rates were (20 .87 ± 1 .09)％ ,(43 .96 ± 1 .08)％ ,(53 .85 ± 1 .08)％ ,(64 .84 ± 1 .06)％ and (74 .72 ± 1 .07)％ ,respectively ,with statistically significant differences among groups (F=25 .321 , P< 0 .01 ) . half maximal inhibitory concentration at 48 h was 343 .47 U/mL . The levels of hydroxyproline in 100 ,200 and 400 U/mL IFNα-1b groups were (7 .48 ± 0 .28) ,(6 .26 ± 0 .17) and (3 .86 ± 0 .20) μg/mL ,respectively ,which were lower than that in control group (8 .47 ± 0 .32) μg/mL .The differences were all statistically significant (t=4 .033 ,10 .564 and 21 .160 ,respective ,all P<0 .05) .The fluorescence intensities of PKCεin 100 ,200 and 400 U/mL IFNα-1b groups were all lower than that of control group .The differences were statistically significant (t=1 .984 ,2 .457 and 7 .771 ,respectively ,all P<0 .05) .The fluorescence intensities of PKCαwere also significantly lower than that of control group (t=9 .232 ,15 .921 and 22 .222 ,respectively ,all P< 0 .01) .With the increase of IFNα-1b level ,the levels of HSC-T6 PKCε,PKCα,β-catenin and survivin were significantly lower than those of control group (t=7 .020 ,24 .562 ,45 .701 and 14 .241 ,respectively ,all P<0 .01) .With the increase of IFNα-1b ,the levels of HSC-T6 PKCε,PKCα,β-catenin and survivin were significantly lower than those of control group (t=9 .564 ,4 .409 ,10 .036 and 6 .794 ,respectively ,all P<0 .01) .Conclusions IFNα-1b can down-regulate the expression of collagen in hepatic stellate cells in a dose-dependent manner ,reduce the expressions of PKCε,PKCα,β-catenin and Survivin ,and inhibit the proliferation of HSC-T6 hepatic stellate cells .

Objective To investigate the efficiency and prognostic factors for the patients with hepatocel-lular carcinoma (HCC) at unresectable early stage when treated with percutaneous microwave ablation. Methods From January 2007 to January 2010 , 105 cases of at unresectable early stage were treated with percutaneous microwave ablation. Complete response rate, major complication rate, overall survival rates, disease-free survival rate were observed and prognostic risk factors were analyzed. Results The complete response rate was 95.7%. The major complication ratewas 3.8%. The 1-, 3-, and 5-year overall survival rates were 97.1%, 66.7%, 46.7%, and the corresponding disease-free survival rates were 82.9%, 48.6%, 31.4%, respectively. Age > 65 year and tumor size > 3 cm were independent risks for disease-free survival. Age > 65 year and recurrence were independent risks for overall survival. Conclusions Percutaneous microwave ablation is a safe and efficient ther-apy for HCC at unresectable early stage.

Objective To identify the types,frequency and risk factors of major complications using microwave ablation (MWA) to treat liver malignancies in a single center.Methods Using the electronic medical record system,patients with liver cancer who were treated with MWA from January 2010 to November 2015 were retrospectively studied,and the risk factors of severe complications were analyzed.Results Of the 7 403 patients who were treated with MWA (12 558 ablations).96 cases experienced severe complications (1.3％) and 5 patients died (0.07％).The complications included liver abscess (n ＝ 34,0.46％),pleural effusion (n ＝ 20,0.27％),bile duct injury (n ＝ 15,0.20％),hemorrhage (n ＝ 6,0.08％),liver failure (n ＝ 6,0.08％),extrahepa-tic organ injuries (n ＝ 5,0.07％),cancerous cells implantation of abdominal walls (n ＝ 2),cardiac arrest (n ＝ 1),vascular thrombosis (n ＝ 1),renal insufficiency (n ＝ 1),and patients with other associated diseases which developed after the MWA therapy (n ＝2).Metastatic liver cancer and earlier treatment of MWA sessions were associated with a higher major complication rate (P ＜ 0.05).Conclnsions MWA is a well-tolerated local treatment for liver cancer,with an acceptably low incidence of severe complications.Liver abscess was the most common postoperative severe complication.The surgeons＇ experience and tumor type were associated with the incidence of severe complications,however,not relavant with the frequency of preoperative ablations.Appropriate measures can be taken to effectively reduce the risk of serious complications.

[Summary] In the treatment of very-early stage hepatocellular carcinoma ( HCC) , several therapies have their own strengths . Liver transplantation, surgical resection, and percutaneous ablation are the most effective procedures for very-early stage HCC.Liver transplantation is difficult to carry out due to lack of donors .Surgical resection and percutaneous ablation are the most commonly used methods with ideal effects .Compared with surgical resection , percutaneous ablation has its obvious advantages in patients with small HCC and senile patients , but the recurrence rate is relatively high .When the above mentioned three methods are not feasible , transarterial chemoembolization is a remedial treatment .Combined use of local therapy is superior to topical therapy alone and suitable for patients with unresectable lesions .Theobserving therapystill needs more clinical studies to confirm its safety and effectiveness .