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With the development of modern liver surgical techniques and the progress of perioperative management,the survival rate after resection of hepatocellular carcinoma has been greatly improved,but the high recurrence and metastasis rate still limits the long-term survival after surgery. Preoperative neoadjuvant therapy has been confirmed to significantly reduce the postoperative recurrence rate and prolong survival in other types of cancer,but there has been a lack of effective systemic therapy for hepatocellular carcinoma for a long time,so the efficacy and regimen of neoadjuvant therapy for hepatocellular carcinoma are still controversial. PD-1/PD-L1 monoclonal antibody combined with anti-angiogenic targeted drugs has become a first-line regimen in systemic therapy for advanced hepatocellular carcinoma. This regimen has definite efficacy and high safety,bringing hope for neoadjuvant therapy of hepatocellular carcinoma. Recently,three clinical trials of neoadjuvant immunotherapy for hepatocellular carcinoma have been published internationally,which preliminarily suggest the efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma and lay a solid foundation for carrying out larger sample clinical studies in the future.
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Humans , Carcinoma, Hepatocellular/pathology , Neoadjuvant Therapy , Liver Neoplasms/pathology , ImmunotherapyABSTRACT
Objective:To evaluate the effect of thymosin alpha 1 on the prognosis of patients with coronavirus disease 2019 (COVID-19).Methods:A retrospective cohort study was performed to collect clinical data of 95 patients treated by Shanghai Aid Medical Team in Wuhan Third Hospital during January 31, 2020 and March 4, 2020, who were confirmed COVID-19. They were divided into two groups according to whether they were treated with thymosin alpha 1 after admission. The 28-day mortality (primary outcome), and 28-ventilator-free-day, lymphocyte count (LYM) level, C-reactive protein (CRP) level (secondary outcomes) were compared between two groups. Survival analysis was performed using the Kaplan-Meier curve. The effect of thymosin alpha 1 on 28-day survival was evaluated with Cox regression model.Results:Among the 95 patients, there were 31 cases in thymosin group and 64 cases in non-thymosin group; 29 patients died 28 days after admission, including 11 cases (35.5%) in thymosin group and 18 cases (28.1%) in non-thymosin group. Kaplan-Meier survival curve showed that thymosin alpha 1 could improve the 28-day survival of patients with COVID-19, but the univariate Cox model analysis showed that the difference was not statistically significant [hazard ratio ( HR) = 0.48, 95% confidence interval (95% CI) was 0.20-1.14, P = 0.098]; multivariate Cox model analysis showed that thymosin alpha 1 was the factor to improve the 28-day mortality ( HR = 0.15, 95% CI was 0.04-0.55, P = 0.004), old age ( HR = 1.10, 95% CI was 1.05-1.15, P < 0.001), accompanied by chronic renal dysfunction ( HR = 42.35, 95% CI was 2.77-648.64, P = 0.007), decrease of LYM at admission ( HR = 0.15, 95% CI was 0.04-0.60, P = 0.007) and the use of methylprednisolone ( HR = 4.59, 95% CI was 1.26-16.67, P = 0.021) were also risk factors for the increase of 28-day mortality. The use of immunoglobulin and antiviral drugs abidol and ganciclovir did not affect the 28-day mortality. After adjustment for age, gender, LYM and other factors, weighted multivariate Cox analysis model showed thymosin alpha 1 could significantly improve the 28-day survival of COVID-19 patients ( HR = 0.45, 95% CI was 0.25-0.84, P = 0.012). In terms of secondary outcomes, no statistical difference (all P > 0.05) was found between two groups in days without ventilator at 28 days after admission (days: 17.97±13.56 vs. 20.09±12.67) and the increase of LYM at 7 days after admission [×10 9/L: -0.07 (-0.23, 0.43) vs. 0.12 (-0.54, 0.41)]. But the decrease of CRP at 7 days after admission in thymosin alpha group was significantly greater than that in non-thymosin group [mg/L: 39.99 (8.44, 82.22) vs. 0.53 (-7.78, 22.93), P < 0.05]. Conclusion:Thymosin alpha 1 may improve 28-day mortality and inflammation state in COVID-19 patients.
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Objective:To analyze the relationship between blood electrolytes and the prognosis of patients with severe coronavirus disease 2019 (COVID-19) and to provide assistance for clinical decision-making.Methods:The clinical data of patients with severe COVID-19 admitted to intensive care unit (ICU) of the Wuhan Third Hospital by the Shanghai aid-Hubei medical team from January 21 to March 4, 2020 were collected. Excluding ineligible patients, 110 patients were finally enrolled. The patients' gender, age, temperature, heart rate, systolic and diastolic blood pressure, clinical symptoms at admission, time of symptom onset, duration of fever, and relevant indicators at admission to ICU (including blood potassium, chloride, sodium, calcium, phosphorus, and magnesium, etc.) and prognosis were analyzed. The patients were grouped by blood potassium or calcium levels or blood potassium/calcium ratio. The Kaplan-Meier survival curves were used to analyze the survival of patients in each group. The relationship between the potassium/calcium ratio and the prognosis was analyzed using restricted cubic spline plots. The relationship between each index in the different models and the prognosis was analyzed using Cox regression models.Results:Among 110 severe COVID-19 patients, 78 cases survived, and 32 cases died. Compared with the surviving group, patients in the death group had higher blood potassium levels [mmol/L: 4.25 (3.80, 4.65) vs. 3.90 (3.60, 4.20), P < 0.05] and lower blood calcium levels (mmol/L: 2.00±0.14 vs. 2.19±0.18, P < 0.05). The Kaplan-Meier survival curves showed that patients in the potassium > 4.2 mmol/L group had a worse prognosis than the potassium < 3.8 mmol/L group and the potassium 3.8-4.2 mmol/L group ( P = 0.011), patients in the calcium > 2.23 mmol/L group had a better prognosis than the calcium < 2.03 mmol/L group and the calcium 2.03-2.23 mmol/L group, and the lower calcium group had a worse prognosis ( P = 0.000 15). Cox regression analysis showed that the hazard ratio ( HR) of blood potassium and calcium were 2.08 and 0.01, respectively, in model 1 (single blood potassium or calcium) and in model 2 (model 1 plus age and gender), the HR of blood potassium and calcium were 1.98 and 0.01 respectively, which were significantly associated with patient prognosis (all P < 0.05). Patients in the group with the potassium/calcium ratio > 1.9 had higher blood potassium levels and a higher proportion of mechanical ventilation, lower calcium levels and lower proportion of survival, and longer time of ICU admission compared with the groups with the potassium/calcium ratio < 1.7 and 1.7-1.9. The Kaplan-Meier survival curves showed that the survival rate of the potassium/calcium ratio > 1.9 group was the lowest ( P < 0.000 1), and there was no statistically significant difference in survival between the potassium/calcium ratio < 1.7 group and the potassium/calcium ratio 1.7-1.9 group. A restricted cubic spline plot corrected for age and gender showed that patients in the potassium/calcium ratio > 1.8 group had HR values > 1. Cox regression analysis corrected for other indicators showed that the potassium/calcium ratio was still associated with patient prognosis ( HR = 4.85, P = 0.033). Conclusions:Blood potassium, calcium, and the potassium/calcium ratio at ICU admission are related to the prognosis of patients with severe COVID-19, and the potassium/calcium ratio is an independent risk factor for the death of patients. The higher the potassium/calcium ratio, the worse the prognosis of patients.
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Objective:To explore the protective effect of hypothermia plus extracorporeal membrane oxygenation(ECMO)on kidney in brain-dead kidney transplant donors.Methods:From July 2017 to July 2018 at Institute of Transplantation Medicine, Hospital No. 923 of PLA, 29 patients with circulatory dysfunction brain death donors fulfilling the organ donation criteria were randomly divided into sub-hypothermia group according to the treatment of extracorporeal membrane oxygenation(body temperature 34.0~35.0℃, 15 cases)and normal temperature group(36.5~37.5℃, 14 cases). Hemodynamic profiles and renal function changes were compared between two groups during ECMO.And renal complications of two groups were followed up.Results:The hemodynamic parameters of two groups remained stable during ECMO period.Heart rate of 5 MO-organs was lower in hypothermia group than that in normal temperature group( P<0.05). Systolic and diastolic pressures before ECMO 3 h-organ acquisition were higher than normal temperature group( P<0.05). No significant difference existed between PaO 2 and normal temperature groups( P>0.05). Donor serum creatinine(SCr)and blood urea nitrogen(BUN)were lower in hypothermia group than in normal temperature group( P<0.05). The postoperative recipient levels of BUN were lower in mild hypothermia group than those in normothermia group( P<0.05)and no significant difference between SCr and normal temperature groups( P>0.05). The postoperative hospital stay was(16.52±3.59)days in mild hypothermia group. And it was lower than that in normal temperature group( P<0.05). Delayed renal function was lower than normal temperature group(3.45% and 21.43%, P<0.05). Conclusions:Mild hypothermia plus ECMO can reduce hemodynamic fluctuations in circulatory unstable donors after brain death, improve renal function and lower the incidence of delayed functional recovery after renal transplantation.
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Zoster sine herpete (ZSH) is one of the atypical clinical manifestations of herpes zoster (HZ), which stems from infection and reactivation of the varicella-zoster virus (VZV) in the cranial nerve, spinal nerve, viscera, or autonomic nerve. Patients with ZSH display variable symptoms, such as neuralgia, however, different from HZ, ZSH show no zoster, which makes clinical diagnosis difficult. ZSH not only causes initial symptoms, such as neuropathic pain in the affected nerve, Bell palsy, and Ramsay Hunt syndrome, but also postherpetic neuralgia and fatal complications such as VZV encephalitis and stroke. The misdiagnosis of ZSH and tardy antiviral treatment may lead to severe ZSH sequelae. We review the publications related to ZSH, especially its diagnosis with VZV DNA and/or anti-VZV immunoglobulin (IgG and IgM). More work about ZSH, especially ZSH epidemiological survey and guidelines for its diagnosis and treatment, are needed because most of the present studies are case reports.
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Objective To evaluate the efficacy of flupentixol and melitracen in optimizing conven-tional treatment for postherpetic neuralgia. Methods Seventy patients of both sexes with thoracolumbar postherpetic neuralgia, were divided into 2 groups ( n=35 each) according to the registration order: pa-tients with odd number were included in control group ( group C) and patients with even number were in-cluded in flupentixol-melitracen group (group D). Patients in group C received conventional treatment: an-ti-epileptic drugs, analgesia with opioids, neurotrophy, paravertebral nerve block and physical therapy. Flupentixol-melitracen 10. 5 mg was taken orally based on the conventional treatment in group D. The time for treatment was recorded. The severity of pain was assessed by using the numeric rating scale, and anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale before treatment and on 3rd and 7th days after treatment. The development of flupenthixol and melitracen-related adverse reactions was recorded during treatment in group D. Results Compared with group C, the numeric rating scale and Hos-pital Anxiety and Depression Scale scores were significantly decreased on 3rd and 7th days after treatment, and the time for treatment was shortened in group D (P<0. 05). No flupenthixol-and melitracen-related ad-verse reactions were found in group D. Conclusion Flupentixol-melitracen can optimize the conventional therapeutic effect for postherpetic neuralgia.
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Objective By analyzing the perioperative management in our hospital to explore the clinical effect and safety of single kidney transplantation from deceased juveniles' donors.Methods We retrospectively analyze 86 cases of kidney transplantations from deceased juveniles' donors in our hospital from 2007 December to 2015 August.Results The success rate of the operations was 100%.The postoperative complications occurred as fellows:7 cases of acute rejection (8.14%);10 cases of drug intoxication (11.62%);21 cases of DGF (24.44%),4 cases of leakage of urine (4.65%),7 cases of lung infection (8.14%).Two cases (2.32%) died after the operation because of serious lung infection,and by corresponding treatment 47 cases recovered after 2-4 weeks.The creatinine level in 37 cases without any complications was 131.88 ± 44.20 μmol/L during discharge.Conclusion With strict selection,the organ from a deceased juvenile donor is safe and practicable.
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Objective To retrieve,appraise and summarize the best evidence of risk assessment for PICC-related venous thrombosis and provide references for establishing relevant assessment tools.Methods British Medical Journal Best Practice,Cochrane Library,JBt Library,Registered Nurses' Association of Ontario (RNAO),National Guideline Clearinghouse (NGC),International Practice Guideline Registry Platform,China Guideline Clearinghouse (CGC),PubMed,EMbase,CNKI and CBM were searched from inception to March,2017,to collect literatures including clinical practice guideline,best practice information sheet,recommended practice and systematic review regarding risk assessment for PICC-related venous thrombosis.Results Eight studies were recruited,including five clinical practice guidelines,and three systematic reviews.Three categories (individual factors,iatrogenic factors,and catheterrelated factors)and totally 18 items of best evidence were summarized.Conclusion It is critical to perform individualized risk assessment for preventing PICC-related venous thrombosis before PICC placement.Medical institutions should establish principles,procedures and practice guidelines for PICC-related venous thrombosis assessment based on best evidence.
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Objective To observe the clinical effect of the maintenance for the liver and kidney function by extra corporeal membrane oxygenation (ECMO) in brain death donor with severe hemodynamic instability.Methods Ninety-nine brain death donors maintained by ECMO were followed up.The criteria for using the ECMO to protect the organ function were as follow:cardiopulmonary resuscitation history (cardiac compression > 20 min);mean arterial pressure (MAP),for Adult <60-70 mmHg,for child <50-60 mmHg,and for infant <40-50 mmHg;cardiac index <2 L/(m2 ·min) (3 h);Large doses of vasoactive drugs,for doparnine 20μg/(kg·min),for (norepinephrine) epinephrine 1.0 μg/(kg· min) (3 h),and for oliguria <0.5 mL/(kg · h);blood biochemical indexes,moderate,severe impairment on acute hepatic and renal function;others,ST-T significant changes in electrocardiogram,and difficult to correct the metabolic acidosis (3 h).The organs were evaluated during their retrieval and as well their evolution after transplantation was evaluated.Results ECMO allowed for the maintenance of hemodynamic stability before organ procurement.A total of 99 cases receiving ECMO maintenance were collected,equal to100 % of the total donation cases (100%).198 kidneys,and 99 livers were procured from these donors meanwhile 15 kidneys and 42 livers respectively were discarded as theywere shown in a macroscopic evaluation.177 of the procured kidneys were transplanted.DGF of kidney transplantation was observed in 20.9%of the cases.Acute rejection incidence was 12.99%.Transplanted kidneys and recipient survival rate was 96.1%/99.3% for one year,94.7%/97.8% for 3 years,and 93.6/97.8% for 4 years,respectively.There was no significant difference in patient or graft survival between the group with ECMO and the group without ECMO.Conclusion ECMO in the brain dead donors with severe circulatory dysfunction allows to avoid organ donors loss and obtain good quality kidneys and livers with excellent graft survival after transplantation.
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BACKGROUND:Delayed graft function (DGF) occurs frequently in kidney transplants from donation after cardiac death if creatinine level is high in kidney recipients. OBJECTIVE:To analyze the clinical effects of renal transplantation with kidneys from donors dying of cardiac death in organophosphate poisoning. METHODS:Data were col ected from kidney transplants from two donors dying of cardiac death in organophosphate poisoning. After some donor maintenance, donor organ were obtained and perfused with impulse type machine. Recipients were treated with intervention of immunity induction, anti-rejection drugs and infection prevention drugs during and after renal transplantation. Pathological data of donor kidney zero needle biopsy, DGF after kidney transplantation, complication rate (such as acute rejection), renal al ograft recovery situation, the survival rate of recipients and kidney transplants were col ected and analyzed. RESULTS AND CONCLUSION:Needle biopsy results from four donor kidneys showed that glomerular morphology was normal, but there were edema and degeneration in kidney tubules in some degree. Donor DGF rate was 75%(3/4), acute rejection rate was 0%(0/4), perioperative period donor kidney and recipient survival rate were 100%(4/4). Al recipients showed a good result of transplanted kidney, their creatinine and urea nitrogen were at low level, and had no proteinuria. One recipient died of severe pulmonary infection 4 months after surgery. For some organophosphate poisoning donors dying of cardiac death, donor kidney quality can be improved by suitable donor maintenance and high-quality donor kidney preservation using machine perfusion. Kidney transplants from donors dying of cardiac death in organophosphate poisoning who receive the maintenance of organ function may be a promising candidate for renal transplantation due to a severe lack of kidney donor sources.
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Objective To summarize the short-term results of simultaneous pancreas-kidney transplantation (SPK) at a single center in China.Methods SPK was performed on 12 consecutive patients from Jan.2010 to July 2014.All patients had long-standing insulin-dependent diabetes mellitus (IDDM) and subsequent renal failure.Bladder drainage (BD) of exocrine secretion was used in the 10 cases and enteric drainage (ED) in 2 patients.The patients were treated with quadruple therapy,which included ATG or anti-CD25 monoclonal antibody induction therapy,prednisone,tacrolimus and mycophenolat-mofetil (MMF).Results The SPK was performed successfully in 10 cases.One patient accepted re-pancreas transplantation due to necrotizing pancreatitis.One patient suffered hemorrhage of bladder,accepted 3 times of embolization therapy and died due to lung infection.Ten patients achieved excellent renal function and euglycemia,and no further insulin treatment was given in 9.5 ± 4.2 days posttransplant.Fasting plasma glucose returned to normal in 14.2 ± 5.1 days.Serum creatinine returned to normal in 10.4 ± 6.5 days.The mean hospital stay was 21.4 ± 7.3 days.One biopsy-proven renal rejection episodes occurred in 14 days postoperation.Main complications included wound infections on the side of pancreatic graft,lymphorrhagia,tacrolimus toxicity and urinary tract infection.Conclusion SPK is an effective therapy of ESRD.Donated graft protection system foundation,refinement and individualized treatment posttransplantion may be the key factors for successful SPK.
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Abstract:By using PVX derived vector pGR107, the effect of BYDV-MP nuclear localization signal on the movement of PVX was studied. BYDV-MP was cloned into pGR107 using GFP as an indicator. BYDV-MP was then shown to induce the systemic infection and exacerbate the symptom of PVX through infecting Nicotiana benthamiana. When the PVX gene encoding 25kD protein, which functioned as a systematic movemnet protein,was deleted and the above experiment was repeated, the result showed that BYDV-MP could compensate the systemic movement of PVX. A serial mutants with substitutions on the fifth, sixth and seventh amino acids of BYDV-MP nuclear localization signal was further constructed. It was found that the mutants at the fifth, sixth amino acids in BYDV-MP nuclear localization signal could only delay or weaken systemic movement of PVX whereas the mutant at seventh amino acid could entirely inhibit systemic movement of PVX.
Subject(s)
Amino Acid Sequence , Green Fluorescent Proteins , Genetics , Luteovirus , Physiology , Molecular Sequence Data , Nuclear Localization Signals , Chemistry , Physiology , Plant Viral Movement Proteins , Physiology , Potexvirus , Genetics , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of replication-competent adenovirus-mediated interleukin-12 gene to chemotherapeutic sensitivity on gastric cancer cell.</p><p><b>METHODS</b>Replication-competent adenovirus and replication-competent adenovirus- mediated interleukin- 12 gene was constructed and expanded separately. The mortality of gastric cancer cell caused by the CNHK200- mIL- 12, Onyx- 015 in combination with different dosages of chemotherapeutic agents were evaluated by MTT assay at the same viral titer with a series of different dosages of chemotherapeutic agent,or at a series of different viral titers with the same dosage of chemotherapeutic agent. The curative effect to the xenografts gastric tumor in nude mouse was also observed by two viruses solely or together with 5-Fu.</p><p><b>RESULTS</b>The lytic activity of replication-competent adenovirus to gastric cancer cell line SGC-7901 was relatively poor at MOI value of 0.5, but it could be improved significantly when combined with chemotherapeutic agents of ADM, 5-Fu or CAP compared to the simple chemical therapy (P< 0.05). Chemotherapeutic agent 5- Fu could not effectively kill SGC-7901 when used at a relatively low dosage of 10microg/ml,whereas its activity could be improved when combined with a replication-competent adenovirus,and the killing rate was much higher than that with replication-competent adenovirus solely (P< 0.05). The gastric tumor xenografts was prevented and killed by replication adenovirus solely or combined with 5-Fu.</p><p><b>CONCLUSION</b>The replication- competent adenovirus- mediated interleukin- 12 gene can increase the chemotherapeutic sensitivity on gastric cancer cell. There is synergetic effect between the replication adenovirus and the chemotherapeutic agents in killing gastric cancer cell.</p>
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Animals , Humans , Male , Mice , Adenoviridae , Genetics , Cell Line, Tumor , Drug Screening Assays, Antitumor , Genetic Therapy , Interleukin-12 , Genetics , Mice, Inbred BALB C , Stomach Neoplasms , Drug Therapy , Viral Vaccines , Virus ReplicationABSTRACT
This paper introduces a pathological information network and image analysis system designed by ourselves. The system offers an efficient means for modern medical diagnosis and treatment, teaching, research and management in the department of pathology.