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Objective To explore the diagnosis and clinical characteristics of atypical severe pneumonia caused by Chlamydia abortus(C.abortus).Methods Clinical data of 4 patients diagnosed with atypical severe pneumonia caused by C.abortus in a hospital from January 2021 to November 2022 were collected.Clinical characteristics,dia-gnosis and treatment,and precautions of the disease were comprehensively analyzed.Results All 4 patients were male,aged 63-73 years old,with acute onset,high fever,cough and expectoration.Three patients had a history of contact with poultry,one patient had a history of contact with abortion goat.The interval between the emerging of clinical symptoms and the onset of acute respiratory failure in 4 patients was 1-6 days,and the oxygenation index(PaO2/FiO2)at admission was less than 200 mmHg,which gradually decreased with the progression of the disease,active support with a ventilator was necessary.Two patients had an increase in white blood cell count,4 had an in-crease in neutrophil percentage,3 had a mild decrease in platelet count.Among 4 patients,2,2,3 and 4 patients showed elevated levels of aspartate aminotransferase,alanine aminotransferase,creatine kinase,and serum creati-nine respectively,2 patients had mild hyponatremia,4 patients showed significant increase in C-reactive protein,procalcitonin,and interleukin-6 levels.Four patients'chest CT findings showed main involvement of single or mul-tiple lung lobes,with exudation and consolidation,and later involvement of multiple lobes of lung.The metageno-mic next-generation sequencing of bronchoalveolar lavage fluid detected the DNA sequence of C.abortus.Based on the clinical manifestations,contact history,chest CT,and metagenomic next-generation sequencing results of 4 pa-tients,the diagnosis was C.abortus.atypical severe pneumonia.After timely adjustment of the treatment of anti-in-fection regimen based on doxycycline,the patients'condition improved and were discharged.Conclusion C.abor-tus may also cause human pneumonia,which can lead to serious clinical outcome after infection.Patient had a histo-ry of animal contact should be alert to such diseases.Metagenomic next-generation sequencing can detect C.abortus.
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Ketamine is a racemic mixture composed of an equal amount of L-ketamine and D-ketamine. It has a long history of use as an anesthetic, with various effects such as relieving anxiety, reducing suicidal ideation, and treating chronic pain. However, the widespread use of ketamine is limited by adverse reactions such as dizziness, nausea, elevated blood pressure, and potential abuse. Esketamine has been a hot drug on the domestic market in recent years. As a right-handed isomer of ketamine, Esketamine has the aforementioned effects while reducing the incidence of adverse reactions and improving patient tolerance. It has broad application prospects in multiple clinical environments in the fields of psychotherapy and anesthesia. Therefore, this article provides a review of the application and pharmacological characteristics of ketamine during the perioperative period, briefly describing the pharmacological effects and possible mechanisms of ketamine, and introduces the clinical application progress of ketamine in sedation, analgesia, and anti anxiety and depression during the perioperative period. This article also explores the application prospects of ketamine in the perioperative period, in order to provide reference and guidance for the promotion and application of ketamine, and to provide new research directions.
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Objective:To investigate the effect of multi position prone position latex pad in patients with severe acute respiratory distress syndrome undergoing prone position ventilation, aiming to improve the effect of oxygenation therapy and reduce the complications associated with prone ventilation.Methods:A randomized controlled trial was used to select 80 patients with prone ventilation with severe acute respiratory distress syndrome who were admitted to the ICU of Yancheng First People ′s Hospital from February 2020 to February 2022 by convenient sampling method. The random number method was used to divide into experimental group and control group, with 40 cases in each group. The control group used soft pillow cushions for traditional prone ventilation, and the experimental group used homemade multi-site prone latex pads for prone ventilation. The effects of oxygenation therapy (oxygenation index and PaCO 2), the incidence of complications (pressure injury, artificial airway tube slippage, artificial airway tube bending) and nursing workload (length of turning over and total treatment time) were compared between the two groups. Results:After the intervention, the oxygenation index and PaCO 2 in the experimental group was (265.79 ± 21.15), (31.52 ± 3.43) mmHg (1 mmHg=0.133 kPa) respectively, and the control group was (177.43 ± 17.76), (39.73 ± 4.80) mmHg respectively and the differences between the two groups were statistically significant ( t=15.43, 10.17, both P<0.05). The incidence of pressure injury and artificial airway tube bending in the experimental group was 7.5% (3/40) and 0 respectively, and the control group was 37.5% (15/40) and 20.0% (8/40) respectively, and the differences between the two groups were statistically significant ( χ2=10.32, 8.89, both P<0.05). The incidence of artificial airway tube slippage in the experimental group and the control group was 0 and 7.5% (3/40) respectively, and there was no significant difference between the two groups ( χ2=3.12, P>0.05). The duration and total treatment duration of prone turning in the experimental group was (3.56 ± 0.53) min and (34.47 ± 3.72) h respectively, and the control group was (5.18 ± 0.61) min and (50.22 ± 4.60) h respectively, and the differences between the two groups were statistically significant ( t=6.25, 13.55, both P<0.05). Conclusions:The application of multi position prone position latex pad in patients with severe acute respiratory distress syndrome can significantly improve the oxygenation effect, reduce the incidence of complications and reduce the workload of nursing, which is worthy of clinical application.
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Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H population accounts for only 5% of patients. Previous studies have shown that early-stage MSI-H colorectal cancer patients have a good prognosis, but those with advanced disease have a poor prognosis and are not sensitive to chemotherapy. The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution. Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR). Therefore, for MSI-H patients with a strong intention to preserve anal sphincter and a strict evaluation of cCR after neoadjuvant immunotherapy, the Watch-and-Wait strategy offers an opportunity to preserve sphincter function and improve long-term survival quality in a subset of mid-to-low rectal cancers. Research on adjuvant immunotherapy in the field of colorectal cancer is also in full swing, and the results are worth waiting for.
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Humans , Colonic Neoplasms , Colorectal Neoplasms/therapy , Immunotherapy/methods , Microsatellite Instability , Microsatellite RepeatsABSTRACT
Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.
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Female , Humans , Male , Middle Aged , Colorectal Neoplasms/surgery , Immunotherapy , Neoadjuvant Therapy , Rectal Neoplasms/surgery , Retrospective StudiesABSTRACT
The high failure rate of the new drug development has been well recognized. Relying on the pre-clinical data obtained from animal experiments will inevitably cause a low concordance with human clinical trials, which will eventually lead to new drug development failure. Employing human induced pluripotent stem cells (iPSCs) or adult stem cells to simulate disease models can not only provide an unlimited cell materials, but also faithfully represent the genetic background of a certain disease, when iPSCs or adult stem cells derived from patients with a specific disease genetic variation are applied. In addition, gene editing methods can be used to introduce genetic variants of interest into stem cells to generate disease models. Furthermore, by establishing a cell bank with a population of iPSCs in petri dish, in vitro human genetic studies can be carried out in these cells, with GWAS and QTL studies applied to identify genetic variants that are associated with drug sensitivity or cytotoxicity. These efforts may offer valuable information for the recruitment of suitable patients for clinical trials. Therefore, stem cell-derived disease models can provide valuable resources for the pathophysiological studies of diseases as well as the drug development. In this review, we will briefly introduce the development of the liver disease models derived from stem cells and their applications in disease study and drug development.
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Animals , Humans , Cell Differentiation , Drug Development , Gene Editing , Induced Pluripotent Stem Cells , LiverABSTRACT
Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This study believes that the black organic matter constituting Zha-xun is mainly stored in the rocks. The exudation points of Zha-xun mostly distribute on the cliffs of high mountains, which makes it difficult to evaluate its resource distribution and storage area. This paper was aimed at the exudation environment of Tibetan medicine Zha-xun in Sichuan province and 6 ecological environmental factors of the Zha-xun were determined via the field investigation. Combining with these 6 factors as well as the GIS data of Sichuan province, ArcGIS software was used to extract ideal environmental factors which are suitable for exudation of Zha-xun, including geology types, geomorphological types, altitude, slope, vegetation types, and mean annual temperature. The spatial overlay analyses on the extracted environmental factors were carried out to predict the distribution area of Zha-xun in Sichuan province. Afterwards, field investigation was conducted to verify the prediction. The prediction showed that the exudation spots of Zha-xun in Sichuan province mainly located in 29 counties including 12 in Aba Prefecture, 15 in Ganzi Prefecture, and Muli County and Dechang County in Liangshan Prefecture. The deposit areas of Zha-xun were located in the Triassic, Devonian and Silurian strata and were basically distributed in 9 basins, including Dingqu River, Yalong River, Xianshui River, Dadu River, Suomo River, Minjiang River and Baishui River, characterized by a fragmented patch-like distribution along the mountain ranges, and the exudation spots of Zha-xun were mainly scattered among the rain-free cliffs' concavities of river valleys at a certain altitude. The prediction was consistent with the field investigation results, which suggested that it is possible and feasible to predict distribution of Zha-xun resources based on GIS-analysis. The study may provide a scientific basis for comprehensive investigations into Zha-xun's distribution and formation mechanism, thus promoting rational development and utilization of Zha-xun resources.
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China , Geographic Information Systems , Geology , Medicine, Tibetan Traditional , Medicine, Traditional , TemperatureABSTRACT
Objective To estimate sex based on patella measurements of Sichuan Han population by computed tomography three-dimensional volume reconstruction technique, and to explore the application value of patella in sex estimation. Methods CT three-dimensional volume reconstruction images of patella of 250 individuals were collected, the four measurement indicators including patellar length, patellar width, patellar thickness, and patellar volume were measured. The t-test was used to determine measurement indicators with sex differences. Fisher discriminant analysis was used to establish the sex discriminant function and the prediction accuracy was calculated by leave-one-out cross validation. Results The sex differences of the four measurement indicators had a statistical significance (P<0.05). The accuracy rate of the univariate discriminant function established by the patellar length was the highest (82.0%). The accuracy rates of the all indicators discriminant function and the stepwise discriminant function were 80.4% and 81.6%, respectively. Conclusion It is feasible and accurate to estimate sex of Sichuan Han population by patella measurements with CT three-dimensional volume reconstruction technique. The method may be used as an alternative for sex estimation of Sichuan Han population when other bones with higher accuracy are not available.
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Female , Humans , Male , Discriminant Analysis , Forensic Anthropology , Imaging, Three-Dimensional , Patella/diagnostic imaging , Sex Determination by Skeleton , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE@#To establish the drug-resistant cell lines of hepatocellular carcinoma (HCC) induced by sorafenib, and to screen out the high expression genes in drug-resistant cell lines of HCC induced by sorafenib, then to explore the genes related to sorafenib resistance in hepatocellular carcinoma.@*METHODS@#The human PLC and Huh7 cell lines were obtained, then the PLC and Huh7 drug-resistant cell lines were induced with sorafenib by using intermittent induction in vitro. CCK8 assay was used to detect the IC50 value of sorafenib for evaluation of drug sensitivity of hepatocellular carcinoma cell lines in PLC and Huh7. All the up regulated genes in PLC and Huh7 drug-resistant cell lines induced by sorafenib were screened out using high-throughput cDNA sequencing (RNA-Seq), Ualcan database was used to analyze the correlations between the up regulated genes in PLC and Huh7 drug-resistant cell lines induced and four clinical biological characteristics of hepatocellular carcinoma, including the gene expressions between normal samples and tumor samples, tumor stage, tumor grade, and patient overall survival, to find the genes that might be involved in the mechanism of sorafenib resistance of hepatocellular carcinoma.@*RESULTS@#All the up regulated genes detected by the using high-throughput cDNA sequencing (RNA-Seq) in PLC and Huh7 drug-resistant cell lines were further screened out by following conditions:(1) genes co-expressed in PLC and Huh7 drug-resistant cells induced by sorafenib, (2) the fold change was more than 4 times and the difference was statistically significant (P <0.05), the top 12 up regulated genes in PLC and Huh7 drug-resistant cell lines were found, which were TPSG1, CBX4, CLC, CLEC18C, LGI4, F2RL1, S100A6, HABP2, C15ORF48, ZG16, FOLH1, and EPCAM. Compared with the correlations between the twelve genes and the clinical biological characteristics by Ualcan database, the potentially significant gene CBX4 was screened out.@*CONCLUSION@#The human PLC and Huh7 drug-resistant cell lines of hepatocellular carcinoma induced by sorafenib were successfully established. CBX4, the gene related to sorafenib resistance in hepatocellular carcinoma, was screened out by the high-throughput cDNA sequencing (RNA-Seq) and further analysis using Ualcan database, which is providing a powerful basis for further research on the mechanism of sorafenib resistance of hepatocellular carcinoma.
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Humans , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Ligases , Liver Neoplasms/drug therapy , Polycomb-Group Proteins , Serine Endopeptidases , Sorafenib/therapeutic useABSTRACT
Lynch syndrome (LS), an autosomal dominantly inherited disease previously known as hereditary non-polyposis colorectal cancer (HNPCC), leads to a high risk of colorectal cancer (CRC) as well as malignancy at certain sites including endometrium, ovary, stomach, and small bowel (Hampel et al., 2008; Lynch et al., 2009). Clinically, LS is considered the most common hereditary CRC-predisposing syndrome, accounting for about 3% of all CRC cases (Popat et al., 2005). LS is associated with mutations of DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, PMS2, and EPCAM (Ligtenberg et al., 2009; Lynch et al., 2009), which can trigger a high frequency of replication errors in both microsatellite regions and repetitive sequences in the coding regions of various cancer-related genes. Immunohistochemistry (IHC) tests followed by genetic analysis of these mutations play a significant role in diagnosis, treatment determination, and therapeutic response prediction of LS (Lynch et al., 2009; Alex et al., 2017; Ryan et al., 2017). Here, we report substitution of one base-pair in exon 1 of MLH3 (c.1397C>A) and a frameshift mutation in exon 19 of MLH1 (c.2250_2251ins AA) in a 43-year-old Chinese male with an LS pedigree.
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Adult , Female , Humans , Male , Asian People/genetics , China , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Exons , Frameshift Mutation , Germ-Line Mutation , MutL Protein Homolog 1/genetics , MutL Proteins/genetics , PedigreeABSTRACT
BACKGROUND: We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA in predicting EPCH and ENCH. METHODS: We enrolled 492 consecutive patients: 49 with EPCI, 243 with EPCH, 101 with ENCI, and 99 with ENCH. HBcrAg was detected by chemiluminescent enzyme immunoassays. HBsAg and HBeAg were detected by chemiluminescent microparticle immunoassays. HBV DNA was detected by real-time PCR. Predictive performance of HBcrAg, HBsAg, and HBV DNA was evaluated using ROC curves. RESULTS: Areas under ROC curves (AUCs) of HBcrAg, HBsAg, and HBV DNA for predicting EPCH were 0.738, 0.812, and 0.717, respectively; optimal cutoffs were ≤1.43×105 kU/mL, ≤1.89×104 IU/mL, and ≤3.97×107 IU/mL, with sensitivities and specificities of 66.3% and 77.6%, 65.0% and 93.9%, and 60.5% and 79.6%, respectively. AUCs of HBcrAg, HBsAg, and HBV DNA for predicting ENCH were 0.887, 0.581, and 0.978, respectively; optimal cutoffs were >26.8 kU/mL, >2.29×102 IU/mL, and >8.75×103 IU/mL, with sensitivities and specificities of 72.7% and 95.1%, 86.9% and 39.6%, and 89.9% and 92.1%, respectively. CONCLUSIONS: HBsAg and HBV DNA were the best predictors of EPCH and ENCH, respectively. HBcrAg is an important surrogate marker for predicting EPCH and ENCH.
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Humans , Area Under Curve , Biomarkers , DNA , Hepatitis B e Antigens , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B , Hepatitis B, Chronic , Hepatitis , Hepatitis, Chronic , Immunoassay , Immunoenzyme Techniques , Real-Time Polymerase Chain Reaction , ROC CurveABSTRACT
BACKGROUND@#A correct thyroid function reference range is important for the accurate diagnosis of thyroid disease during pregnancy. However, there is no consensus on whether thyroid function reference ranges in Chinese population should follow the America Thyroid Association (ATA) guidelines. This study aimed to establish a thyroid function reference range more suited to the Chinese population by evaluating the current thyroid function reference range in pregnant Chinese women and comparing it to the ATA guidelines.@*METHODS@#A total of 52,027 pregnant women were enrolled from January 2013 to December 2016. Thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels were tested during the first and third trimesters of pregnancy. Reference ranges of TSH and FT4 were established from the 2.5th and 97.5th percentiles of the TPOAb-negative population of women. The Mann-Whitney U test was used to compare thyroid hormones between the TPOAb-positive and TPOAb-negative groups.@*RESULTS@#We obtained that the TSH reference ranges were 0.03 to 3.52 mU/L and 0.39 to 3.67 mU/L, and the FT4 reference ranges were 11.7 to 19.7 pmol/L and 9.1 to 14.4 pmol/L, in the first and third trimester, respectively. If we used the 2011 ATA criteria about 7.0% and 4.0% pregnant women would be over diagnosed in first and third trimester, respectively, compared with local population thyroid hormone reference. When we compared our local criteria with the new 2017 ATA criteria, about 1.2% and 0.8% pregnant women would have a missed diagnosis in first and third trimester, respectively.@*CONCLUSIONS@#Based on our data, which is in line with the current ATA guidelines, a population-based thyroid function reference range would be the first choice for diagnosis of thyroid disease during pregnancy in China. In case such population-based thyroid function reference ranges are unavailable in the east of China, our reference ranges can be adopted, if the same assay is used.@*TRIAL REGISTRATION@#www.chictr.org.cn (No. ChiCTR1800014394).
Subject(s)
Adult , Female , Humans , Pregnancy , Young Adult , Asian People , Iodide Peroxidase , Metabolism , Thyroid Gland , Metabolism , Thyrotropin , Metabolism , Thyroxine , MetabolismABSTRACT
Objective To summarize the efficacy and safety of covered metal stents joint nasobiliary drainage in treated with ERCP-related Ⅲ Stapfer bile duct perforation. Method Covered metal stent were immediately placed with patients for ERCP-related III Stapfer bile duct perforation. Then, nasobiliary drainage were placed. The stents were removed after 2 ~ 4 weeks. Result 6 patients were all improved, and no surgical patients. The effective rate was 100.00%. No stent related complications occurred. The symptoms of abdominal infection occurred in 1 patient during hospitalization, the rate was 16.67%. Conclusion The method of treatment for ERCP-related III Stapfer bile duct perforation was safe and effective, it was worthy of clinical popularization and application.
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PURPOSE: This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). MATERIALS AND METHODS: RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. RESULTS: The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. CONCLUSION: CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.
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Humans , Cell Line , Colorectal Neoplasms , DNA Damage , Genes, vif , Neoplasm Metastasis , Polymerase Chain Reaction , Radiation Tolerance , Radiation, Ionizing , Radiotherapy , Rectal Neoplasms , RNA Interference , RNA, Messenger , Sequence Analysis, RNA , Therapeutic UsesABSTRACT
Objective To compare the clinical efficacy and safety of meropenem administered by standard 30-minute infusion or prolonged 3-hour infusion regimen in treatment of hospital acquired pneumonia (HAP) in elderly patients,and evaluate the effect of augmented renal clearance on clinical efficacy.Methods An open-label randomized controlled clinical trial was conducted.A total of 40 elderly patients (≥65 years of age) with HAP requiring meropenem therapy were enrolled from September 1,2015 to August 31,2016.The patients were randomly assigned to receive meropenem 1.0 g in 100 mL ot 0.9% NaCl solution by constant-rate continuous intravenous infusion over 3 hours (study group,n=20) or by constant-rate intravenous infusion over 30 minutes (control group,n=20),every 8 hours,for at least 7 days.Clinical efficacy and safety were compared between groups.According to the level of creatinine clearance (Ccr),the 40 patients were further divided into group A1 [Ccr ≥ 130 (mL/min)/1.73 m2] and A2 [Ccr< 130 (mL/min)/1.73 m2].The patients with Ccr≥ 130 (mL/min)/1.73 m2 in control group belonged to group B1,and those in study group belonged to group B2.Clinical efficacy was compared between group A1 and A2,and between group B1 and B2.Results The clinical cure rate was 70.00% (14/20) in study group and 50.00% (10/20) in control group (P<0.05).The 28-day survival rate was 85.00% (17/20) in study group and 65.00% (13/20) in control group (P<0.05).The clinical pulmonary infection score (CPIS) was improved significantly in study group (reduction of 2.88±2.51) than in control group (reduction of 1.25 ± 1.67) (P< 0.05).Procalcitonin (PCT) level was more improved in study group [reduction of (2.43± 0.68) μg/L] than in control group [reduction of (1.05±0.27) μg/L] (P<0.05).The duration of meropenem treatment and days of hospital stay did not show significant difference between study group and control group (P>0.05).The common adverse reactions were transient elevation of serum transaminases and diarrhea in both groups.The incidence of adverse reactions did not show significant difference between groups (P>0.05).Further analysis indicated that the clinical cure rate was 44.44% (4/9) in group A1 and 64.52% (20/31) in group A2 (P<0.05).The 28-day survival rate was 66.67% (6/9) in group A1 and 77.42% (24/31) in group A2 (P<0.05).CPIS reduction was 1.62±1.61 in group A1 and 2.19±2.2 in group A2 (P<0.05).The reduction of PCT level was (1.41 ±0.39) μg/L in group A1 and (1.84±0.5) μg/L in group A2 (P<0.05).The duration of meropenem treatment and days of hospital stay did not show significant difference between group A1 and group A2.The clinical cure rate was 1/4 in group B1 and 3/5 in group B2 (P<0.05).The 28-day survival rate was 2/4 in group B1 and 4/5 in group B2 (P<0.05).CPIS reduction was 0.68±0.93 in group B1 and 2.56±2.29 in group B2 (P< 0.05).The reduction of PCT level was (0.61 ±0.15) μg/L in group B 1 and (2.21 ± 0.63) μg/L in group B2 (P<0.05).The duration of meropenem treatment and days of hospital stay did not show significant difference between group B1 and group B2 (P>0.05).Conclusions Prolonged intravenous infusion of meropenem over 3 hours provides better clinical efficacy than the standard 30-minute infusion of meropenem in the treatment of HAP in elderly patients without increase of adverse reactions.Augmented renal clearance may reduce the clinical efficacy of meropenem,which can be improved by 3-hour prolonged infusion ofmeropenem.
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Objective:To evaluate the influence of medical insurance payment standard reform on clinical drug use in designated medical institution.Methods:The medical expenses and drug consumption data of provincial level and Fuzhou medical insurance management center 3.31 million is included from April to September of 2016 and the same period of last year were statistically analyzed.The annual drug cost,drug use and the payment standard of med-ical insurance analysis were performed according to the annual statistics.Results: Before and after the reform, the proportion of the payment of standard drugs increased from 22.50%to 64.95%.The top 10 outpatient drugs in pub-lic hospitals and non-public hospitals were changed only in serial number,and after the reform,the cost of outpatient service fee was 73.21%and 39.30%respectively.Meanwhile,the variety and amount of drugs changed greatly of top 10 drugs public hospitals.The increase in drug cost of drugs with joint purchasing price difference was higher,and non-public hospitals were relatively stable.Conclusions: As per the findings of this study, Medicare insurance payment standard reform has significantly affected the choice of drug brands and drug use structure.To focus on the medical insurance payment standard of concentrated purchase of drugs combined with the amount of joint procurement of medicines is beneficial to reduce drug prices.The medical insurance payment standard reform combined with com-prehensive reform of medical and health system measures are much more conducive to play a guiding role.
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Objective To study the effect of ghost red blood cells (GRBCs) on white blood cell (WBC)-mediated adhesion of tumor cells (TCs) on endothelial cells (ECs) in shear flow. Methods GRBCs with hematocrit (Hct) of 20% were added in the parallel plate flow chamber to observe changes in the number of tethered WBCs on ECs, the collision between TCs and adhesive WBCs, and the number of firmly adhered TCs at different shear rates of 62.5, 100, 200 s-1, respectively. Results GRBCs could increase the number of adhered WBCs on ECs and the collision between TCs and adhesive WBCs, and finally enhance the adhesion of TCs on ECs, especially at high shear rate (200 s-1). However, the adhesion efficiency of TCs was not significantly influenced by GRBCs. Conclusions GRBCs in shear flow can promote TC adhesion on ECs, and the research finding will provide a theoretical basis for cancer therapy.
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Objective To study the different effects from different concentration ratios of polymorphonuclear neutrophil (PMN) to tumor cell (TC) on the process of tumor cell adhesion to endothelial cell (EC) in shear flow. Methods PMNs and TCs with different concentration ratios (PMN-TC ratio) were added into the parallel plate flow chamber, and changes in the numbers of transient and accumulative adhered TCs on ECs at different shear rates (50 s-1,100 s-1,200 s-1) were analyzed. Results The transient and accumulative adhesion of TCs on ECs at PMN-TC ratio of 3︰1 significantly increased as compared to that at PMN-TC ratio of 1︰1, especially under high shear flow condition (100 s-1 and 200 s-1). Moreover, in the 5 minute-observation period, the effect of PMN-TC ratio on TC adhered to ECs occurred earlier when the shear rate increased. Conclusions The increase of PMN-TC concentration ratio can promote TC adhesion to ECs in shear flow, and the research findings provide significant references for studying TC metastasis in blood vessels and the target therapy of tumors.
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<p><b>INTRODUCTION</b>Multimodality therapy, including preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy (CCRT) involving XELOX regimen (oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.</p><p><b>METHODS</b>We randomly assigned patients to the TME group (TME without preoperative CCRT) or CCRT + TME group (TME with preoperative CCRT). The primary endpoint was disease-free survival (DFS); the secondary endpoints were overall survival (OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.</p><p><b>RESULTS</b>A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 % (P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 % (P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT + TME groups were 71.3 % and 70.0 % (P = 0.849), respectively. In the TME group, 16 (17.0 %) patients were proven to have pTNM stage I disease after surgery. In the CCRT + TME group, 32 (35.6 %) patients achieved a pathologic complete response (pCR).</p><p><b>CONCLUSIONS</b>Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high pCR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.</p><p><b>CLINICAL TRIAL REGISTRATION NUMBER</b>Chi CTR-TRC-08000122.</p>
Subject(s)
Humans , Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , Chemoradiotherapy , Combined Modality Therapy , Deoxycytidine , Disease-Free Survival , Fluorouracil , Neoadjuvant Therapy , Neoplasm Staging , Organoplatinum Compounds , Prognosis , Prospective Studies , Rectal Neoplasms , Survival RateABSTRACT
ObjectiveTo investigate personal reflections of head nurses on 360-degree performance assessment system. Method Twenty-three head nurses being involved in 360-degree performance assessment received semi-structured interviews and the data were analyzed with content analysis.ResultThe head nurses were positive about the assessment system,believing that the assessment system was helpful for detecting the weak links of daily work and thinking that the assessment indexes varied in weights with different clinical disciplines.ConclusionsThe 360-degree performance assessment was beneficial for ability promotion of head nurses and continuous improvement of nursing quality.Hospital administrators should continuously improve and promote 360-degree performance assessment system.