Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation / 陆军军医大学学报

Objective To investigate the effects of anti-HLA donor-specific antibodies(DSA)and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies,15(21.4％)patients were DSA positive,including 7(46.7％)cases of strong positive,3(20.0％)cases of moderate positive,and 5(33.3％)cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients(P=0.027).For the 6 patients developed graft failure(GF),4 were DSA+which was statistically higher than the DSA-patients(P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF(HR=9.273,95％CI:1.505～57.124,P=0.016).Among the 10 patients(7 strong positive and 3 moderate positive DSA)received desensitization therapy,4 patients received combination desensitization,with a 100％rate of successful transplantation,and 6 received single desensitization,with 4(66.7％)experiencing GF,so the GF rate was obviously lower in the combination than the single desensitization(P=0.008).Conclusion In haplo-HSCT patients,DSA is an important factor leading to implantation delay and GF.While,single desensitization treatment has limited efficacy.In combined DSA desensitization therapy,the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

Effect of application of anti-seizure medications on the development of chronic epilepsy after autoimmune encephalitis / 中华神经科杂志

Objective:To investigate and analyze the use and duration of anti-seizure medications (ASMs) in patients with chronic epilepsy after autoimmune encephalitis (AE), as well as the effect of ASMs use on the formation of this epilepsy to provide relevant evidence for the choice of ASMs in patients with acute seizure or chronic epilepsy after AE.Methods:A retrospective follow-up study was performed on AE patients (including patients with antibody-negative autoimmune limbic encephalitis) diagnosed in the Affiliated Brain Hospital of Nanjing Medical University from December 1, 2013 to October 31, 2022. The dates of the first seizure onset and the chronic epilepsy formation (defined as 1 year after immunotherapy) were recorded. The initial time, types and numbers of ASMs used in acute symptomatic seizure (ASS) and the maintenance time, types and numbers of ASMs in chronic epilepsy period (the continuation or the combined therapy of ASMs) were collected, respectively. A Logistic regression model was used to analyze multi-influencing factors on the formation of chronic epilepsy after AE.Results:A total of 332 patients were enrolled in this study, of whom 32.5% (108/332) with antibody-negative autoimmune limbic encephalitis. In total, 54.8% (182/332) of patients were males, and the age of onset was (40.7±19.7) years. Finally, 81.0% (269/332) of participants manifested ASS, and 57.2% (190/332) developed chronic epilepsy up to the last follow-up. The follow-up time was 1-8 years, with a median of 2 years. All patients received ASMs treatment during ASS period. Among the ASS patients, 48.0% (129/269) were prescribed monotherapy of ASMs, and 52.0% (140/269) were given the combined therapy of ASMs. Of all the patients with ASMs, 70.3% (189/269) were given early ASMs treatment (within 24 hours of the seizure onset), and 29.7% (80/269) were given delayed ASMs treatment. Subsequently, 81.0% (218/269) of the ASS patients continued the ASMs treatment (>6 months), and 19.0% (51/269) stopped use of ASMs. In the chronic epilepsy stage, 79.5% (151/190) of thee epilepsy patients continued ASMs, of whom 37.1% (56/151) were treated with monotherapy, and 62.9% (95/151) were treated with combined therapy. The incidence of chronic epilepsy was 81.3% (65/80) in the delayed ASMs treatment group, higher than the 66.1% (125/189) in the early ASMs treatment group,with statistically significant difference (χ 2=6.189, P=0.013). There were no statistically significant differences in the ASMs types and whether combined therapy of ASMs was used between chronic epilepsy group and non-chronic epilepsy group. The Logistic regression model showed that delayed ASMs treatment ( OR=2.306,95% CI 1.032-6.387, P=0.018), positive anti-neuronal intracellular antibodies ( OR=2.626,95% CI 1.536-9.531, P=0.004,compared with anti- neuronal surface antibodies), abnormal brain magnetic resonance imaging ( OR=9.883,95% CI 3.608-27.071, P<0.001), elevated cerebrospinal fluid protein ( OR=2.874,95% CI 1.115-7.409, P=0.029), and abnormal electroencephalogram ( OR=9.287,95% CI 3.767-22.896, P<0.001) were independent risk factors for chronic epilepsy after AE. Conclusions:The development of chronic epilepsy after AE is associated with the occurrence of ASS and the delayed use of ASMs, but the type of ASMs or whether the combined ASMs therapy is used is not associated with the formation of chronic epilepsy after AE. It is concluded that early ASMs treatment for the AE patients with ASS may reduce the incidence of chronic epilepsy. For AE patients with ASS who have undergone early standardized treatment, long-term, combined ASMs treatment may not be necessary.

46XY simple gonadal hypoplasia: 2 case reports and literature review / 中国综合临床

46XY simple gonadal hypoplasia, also known as Sweyer syndrome, patients often due to primary amenorrhea or pubertal secondary sex characteristics do not develop the doctor, its combined gonadal tumor is more likely, in the treatment process is often recommended prophylactic removal of gonads, postoperative hormone replacement therapy. We describe two patients diagnosed with Sweyer syndrome, one with gonadowlastoma and mature teratoma, and one with nodular Leydig cell hyperplasia and ectopic adrenal tissue, and reviews the literature.

Clinical characteristics and prognostic analysis of newly diagnosed CD5-positive diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To explore the clinical characteristics and prognosis of newly diagnosed CD5-positive diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 19 newly diagnosed CD5-positive DLBCL patients in Tenth People's Hospital of Tongji University and Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine between January 2015 and December 2018 were retrospectively analyzed. Their clinical characteristics and laboratory indexes were observed; Kaplan-Meier method was used for survival analysis, and Cox proportional risk model was used to make multifactor analysis of the prognostic factors.Results:The median age of 19 newly diagnosed CD5-positive DLBCL patients was 63 years (34-76 years). All 19 patients included 13 cases with Ann Arbor Ⅲ-Ⅳ stage; 12 cases with lactate dehydrogenase higher than the normal value limit, 9 cases with international prognostic index scores ≥ 4, 13 cases with B symptoms, 10 cases with Ki-67 positive index ≥ 80%, 15 cases with more than 1 lymph extra nodal organ involvement and 8 cases with tumor mass (mass diameter ≥ 7 cm). The 2-year progression-free survival (PFS) rate was 47.4% and 2-year overall survival (OS) rate was 63.2%. Univariate analysis showed that Ann Arbor stage, tumor mass, lymph extra nodal involvement and ≥ 4 courses of intrathecal injection were associated with OS (all P < 0.05). Multivariate analysis showed that Ann Arbor stage (stage Ⅰ-Ⅱ vs. stage Ⅲ-Ⅳ: HR = 0.158, 95% CI 0.031-0.803, P = 0.026), tumor mass (tumor diameter < 7 cm vs. tumor diameter ≥ 7 cm: HR = 0.076, 95% CI 0.009-0.637, P = 0.018)and ≥ 4 courses of intrathecal injection (yes vs. no: HR = 9.130, 95% CI 1.062-78.157, P = 0.044) were independent influencing factors for OS. Conclusions:Newly diagnosed CD5-positive DLBCL is highly aggressive and susceptible to extra nodal infiltration. Ann Arbor stage Ⅲ-Ⅳ, tumor mass, and not receiving ≥ 4 courses of intrathecal injection are independent risk factors affecting the prognosis of CD5-positive DLBCL patients.

Clinical observation of electroacupuncture combined with Qingyi Xianxiong Decoction in the treatment of acute respiratory distress syndrome due to severe acute pancreatitis / 中华危重病急救医学

Objective:To observe the clinical effect of electroacupuncture combined with Qingyi Xianxiong Decoction on the treatment of acute respiratory distress syndrome (ARDS) caused by severe acute pancreatitis (SAP).Methods:From February 2021 to April 2022, 120 patients with ARDS caused by SAP who were admitted to the department of critical care medicine of Tianjin Nankai Hospital and whose syndrome differentiation belonged to the syndrome of knot chest were selected. They were randomly divided into pure traditional Chinese medicine group and acupuncture medicine group, with 60 cases in each group. The pure traditional Chinese medicine group was received Qingyi Xianxiong Decoction on the basis of conventional western medicine treatment, and the acupuncture medicine group was received electric acupuncture treatment on the basis of the pure traditional Chinese medicine group. The two groups continued to be treated for 7 days. The primary outcome was the ventilator-free days within 28 days after admission to the intensive care unit (ICU), and the secondary outcome measures were mechanical ventilation time, the length of ICU stay, total lenth of hospital stay, time of intra-abdominal pressure recovery, scores of organ function, oxygenation index (PaO 2/FiO 2), serum inflammatory factors, blood amylase, urine amylase, etc. Results:Compared with the pure traditional Chinese medicine group, the ventilator-free days in the acupuncture medicine group within 28 days after admission to the ICU were significantly longer [day: 22.10±2.29 vs. 20.97±2.31, P < 0.05, odds ratio ( OR) = 1.24, 95% confidence interval (95% CI) was 1.053-1.460, P < 0.05]. The time of mechanical ventilation, the length of ICU stay, total length of hospital stay, and recovery time of intra-abdominal pressure were significantly shortened [mechanical ventilation time (days): 5.90±2.29 vs. 7.03±2.31, the length of ICU stay (days): 8.07±1.89 vs. 12.08±2.23, total length of hospital stay (days): 19.55±6.82 vs. 22.28±5.19, recovery time of intra-abdominal pressure (days): 6.05±1.81 vs. 8.45±1.76, all P < 0.05]. The Murray score and bedside index for severity in acute pancreatitis (BISAP) score of the two groups after 7 days of treatment were significantly lower than those before treatment, while PaO 2/FiO 2 was significantly higher than those before treatment, and the Murray score of the acupuncture medicine group after 7 days of treatment was significantly lower than that of the pure traditional Chinese medicine group [score: 0.50 (0.33, 0.75) vs. 1.00 (1.00, 1.33), P < 0.05], PaO 2/FiO 2 was significantly higher than that in the pure traditional Chinese medicine group [mmHg (1 mmHg ≈ 0.133 kPa): 390.75±27.73 vs. 330.02±42.34, P < 0.05]. With the prolongation of treatment time, the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), serum amylase and urine amylase in both groups after treatment continued to decrease, and the levels of the inflammatory factors in the acupuncture medicine group after 7 days of treatment were significantly lower than those in the pure traditional Chinese medicine group [TNF-α (ng/L): 38.20±10.00 vs. 45.35±5.09, IL-6 (ng/L): 0.95±0.44 vs. 7.42±1.39, CRP (mg/L): 8.55±2.79 vs. 36.20±13.97, all P < 0.05]. Subgroup analysis showed that biliary system disease was a risk factor for the duration of mechanical ventilation ≥ 7 days in the treatment of ARDS with acupuncture and medicine ( OR = 2.728, 95% CI was 1.293-5.754). Conclusion:Compared with the pure traditional Chinese medicine, acupuncture combined can better reduce the clinical symptoms of patients with ARDS caused by SAP, promote the recovery of patients, and reduce systemic inflammatory reaction, which is worthy of clinical promotion.

Relationship between SIRT3 and mitochondrial function in mice with endotoxin-induced lung injury / 中华麻醉学杂志

Objective:To evaluate the relationship between silent information regulator 2 homologue 3 (SIRT3) and mitochondrial function in mice with endotoxin-induced lung injury.Methods:Twenty clean-grade healthy adult male wild C57BL/6 (SIRT3 + /+ ) mice, 20 SIRT3 knockout (SIRT3 -/-) mice, weighing 20-25 g, aged 6-8 weeks, were studied.SIRT3 + /+ mice and SIRT3 -/- mice were divided into 4 groups ( n=5 each) according to the random number table method: blank control group (group C, group SIRT3 -/-C), endotoxin-induced lung injury group (group L, group SIRT3 -/-L), endotoxin-induced lung injury plus resveratrol group (group L+ R, group SIRT3 -/-L+ R), and resveratrol group (group R, group SIRT3 -/-R). Resveratrol 15 mg/kg was intraperitoneally injected once a day for 7 consecutive days in L+ R, R, SIRT3 -/-L+ R and SIRT3 -/-R groups, while the equal volume of normal saline was injected in the rest groups.Lipopolysaccharid 15 mg/kg was injected via the tail vein to develop a mouse model of endotoxin-induced lung injury at 30 min after resveratrol injection on 7th day, in L+ R and SIRT3 -/-L+ R groups and at the corresponding time points in L and SIRT3 -/-L groups, while the equal volume of normal saline was injected in the other groups.Blood samples were collected from the orbital venous plexus at 12 h after injection of normal saline or lipopolysaccharid for determination of serum total oxidation state (TOS) and total antioxidant state (TAS) levels by the xylenol orange method and ABTS colorimetric method, and the oxidative stress index (OSI) was calculated.After the mice were sacrificed, the lung tissues were taken for microscopic examination of the pathological changes which were scored and for determination of the mitochondrial membrane potential (MMP) (by JC-1 method), cellular oxygen consumption rate (OCR) (by the specific fluorescent probe method), and expression of SIRT3 (by Western blot). Results:Compared with group C or group SIRT3 -/-C, the lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in L, L+ R, SIRT3 -/-L and SIRT3 -/-L+ R groups ( P<0.05). Compared with group L, the lung injury score, serum TOS concentration and OSI were significantly decreased, TAS concentration, MMP and OCR were increased, and SIRT3 expression was up-regulated in group L+ R, and lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in group SIRT3 -/-L ( P<0.05). Compared with group L+ R, the lung injury score, serum TOS concentration and OSI were significantly increased, the TAS concentration, MMP and OCR were decreased, and the expression of SIRT3 was down-regulated in group SIRT3 -/- L+ R ( P<0.05). There was no significant difference in the indicators mentioned above between group SIRT3 -/-L+ R and group SIRT3 -/-L ( P>0.05). Conclusions:Down-regulation of SIRT3 expression can lead to impaired mitochondrial function, which is involved in the pathophysiological mechanism of endotoxin-induced lung injury.

A retrospective study of cisatracurium besilate-assisted treatment of severe acute pancreatitis complicated with intraabdominal hypertension / 中华麻醉学杂志

The clinical data of patients with severe acute pancreatitis complicated with intraabdominal hypertension or abdominal compartment syndrome admitted to our Department of Critical Care Medicine from January 1, 2018 to October 1, 2021 were collected and analyzed.Patients were divided into a conventional treatment group and conventional treatment plus IV infusion of cisatracurium besilate group (muscle relaxation group). A prediction model of treatment propensity score was developed for paired screening, with 31 cases in each group.The conventional treatment group adopted conventional basic treatment methods such as gastrointestinal decompression, spasmolysis and analgesia, fluid therapy, inhibition of gastric acid, suppression of parenzyme, nutritional support, mechanical ventilation, and enemata.In muscle relaxation group, cisatracurium besilate was intravenously infused on the basis of routine treatment with the initial dose of 0.15 mg/kg given to facilitate endotracheal intubation, followed by continuous intravenous infusion at 1-3 μg·kg -1·min -1, and the dose was adjusted according to the patient′s basic vital signs and clinical effects.The primary outcome was survival rate.Secondary outcome measures were changes in intraabdominal pressure, oxygenation index, the number of defecation, volume of defecation, and urination volume before treatment and on 7, 14 and 20 days of treatment.and the recovery time of bowel sounds, length of mechanical ventilation, time of intensive care unit treatment, and total hospitalization costs.Compared with conventional treatment group, the survival rate was significantly increased, the intraabdominal pressure was decreased on 7, 14 and 20 days of therapy, the oxygenation index was increased, the number of defecation and volume of defecation were increased on 7 and 14 days of therapy, urinary volume was increased before treatment and on day 7 of therapy, the recovery time of intestinal sound was significantly shortened ( P<0.05), and no significant change was found in urinary volume on days 14 and 20 of therapy, length of ventilation, time of intensive care unit treatment, and total hospitalization costs in muscle relaxation group ( P>0.05). In conclusion, cisatracurium besilate can improve oxygenation, promote the recovery of intestinal function and improve the survival rate when used to assist the treatment in the patients with severe acute pancreatitis complicated with intraabdominal hypertension.

Serum levels of complement B and D in patients with diabetic peripheral neuropathy and their correlation / 中国医师杂志

Objective:To investigate the serum level and significance of complement factor B (CFB) and complement factor D (CFD) in patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN).Methods:From October 2019 to October 2020, 110 patients with T2DM in the endocrinology department of Affiliated Hospital of Jining Medical College were divided into DPN group ( n=60) and simple T2DM group ( n=50) according to whether or not DPN was combined. In addition, 52 cases of physical examination population in the physical examination center in the same period were selected as the normal control group ( n=52). The serum levels of CFB, CFD and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA). The correlation between CFB, CFD and clinical indexes was analyzed, and the influencing factors of DPN were analyzed by logistic regression. Results:The serum levels of CFB and CFD in DPN group were higher than those in T2DM group and normal control group [CFB: (845.43±101.10)μg/ml vs (792.19±116.59)μg/ml, (739.20±123.43)μg/ml, P<0.05], [CFD: (491.71±41.03)mg/L vs (467.58±45.16)mg/L, (445.16±50.47)mg/L, P<0. 05]. Pearson correlation analysis showed that the serum level of CFB was positively correlated with glycosylated hemoglobin (HbA 1c), fasting plasma glucose (FPG) and TNF-α (all P<0.05) and negatively correlated with triiodothyronine (FT3) and total bilirubin (TBIL) (all P<0.05). Serum CFD level was positively correlated with systolic blood pressure, HbA 1c, FPG and TNF-α (all P<0.05), but negatively correlated with FT3 and TBIL (all P<0.05). Logistic regression analysis showed that CFB and CFD were still influential factors for the occurrence and development of DPN after excluding confounding factors such as systolic blood pressure, HbA 1c, FPG, FT3, DBIL, TBIL and TNF-α. Conclusions:(1) Serum CFB and CFD levels were significantly increased in DPN patients, suggesting that CFB and CFD may be involved in the occurrence and development of DPN. (2) Serum TNF-α level was significantly increased in DPN patients, confirming the role of TNF-α in the pathogenesis of DPN.

SARS-Cov-2-, HIV-1-, Ebola-neutralizing and anti-PD1 clones are predisposed

Antibody repertoire refers to the totality of the superbly diversified antibodies within an individual to cope with the vast array of possible pathogens. Despite this extreme diversity, antibodies of the same clonotype, namely public clones, have been discovered among individuals. Although some public clones could be explained by antibody convergence, public clones in naive repertoire or virus-neutralizing clones from not infected people were also discovered. All these findings indicated that public clones might not occur by random and they might exert essential functions. However, the frequencies and functions of public clones in a population have never been studied. Here, we integrated 2,449 Rep-seq datasets from 767 donors and discovered 5.07 million public clones - ~10% of the repertoire are public in population. We found 38 therapeutic clones out of 3,390 annotated public clones including anti-PD1 clones in healthy people. Moreover, we also revealed clones neutralizing SARS-CoV-2, Ebola, and HIV-1 viruses in healthy individuals. Our result demonstrated that these clones are predisposed in the human antibody repertoire and may exert critical functions during particular immunological stimuli and consequently benefit the donors. We also implemented RAPID - a Rep-seq Analysis Platform with Integrated Databases, which may serve as a useful tool for others in the field.

The analysis of the long-term impact of SARS-CoV-2 on the cellular immune system in individuals recovering from COVID-19 reveals a profound NKT cell impairment

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects millions of people and killed hundred-thousands of individuals. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remained to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19 convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2 unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of Annexin V and 7-AAD double positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies, TIM-3 expression on CD4 and CD8 T cells, as well as PD-L1 expression on B cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by GzmB expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully capable to proliferate and produce effector cytokines upon TCR stimulation. Collectively, we provide the first comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.

Safety of Breastfeeding in Mothers with SARS-CoV-2 Infection

BackgroundThe outbreak of Coronavirus Disease 2019 (COVID-19) is threatening a surging number of populations worldwide, including women in breastfeeding period. Limited evidence is available concerning breastfeeding in women with COVID-19. MethodsTwenty-three pregnant women and puerperae were enrolled in the study. To evaluate the effect of breastfeeding on SARS-CoV-2 transmission, the presence of SARS-CoV-2, IgG and IgM in breast milk, maternal blood and infant blood were assessed. Feeding patterns were also recorded in follow-up. ResultsNo positive detection for SARS-CoV-2 of neonates was found. All breast milk samples were negative for the detection of SARS-CoV-2. The presence of IgM of SARS-CoV-2 in breast milk was correlated with maternal blood. The results of IgG detection for SARS-CoV-2 were negative in all breast milk samples. All the infants were in healthy condition while six of them were fed with whole or partial breast milk. Eight infants received antibody test for SARS-CoV-2 in one month after birth and the results were all negative. ConclusionFindings from this small number of cases suggest that there is currently no evidence for mother-to-child transmission via breast feeding in women with COVID-19 in the third trimester and puerperium.

Management of a colon cancer patient complicated with COVID-19 / 浙江大学学报·医学版

OBJECTIVE@#To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19).@*METHODS@#The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed.@*RESULTS@#The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice.@*CONCLUSIONS@#The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

Management of a colon cancer patient infected with corona virus disease 2019 / 浙江大学学报·医学版

OBJECTIVE@#To explore the feasibility of surgical treatment for cancer patients complicated with corona virus disease 2019 (COVID-19).@*METHODS@#The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed.@*RESULTS@#The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice.@*CONCLUSIONS@#The case indicates that it may feasible to undergo radical tumor surgery for cancer patients with COVID-19 after the virus nucleic acid testing turns negative and more studies are needed to confirm this conclusion.

Role of endogenous heme oxygenase-1/carbon monoxide signaling pathway in endoplasmic reticulum stress during endotoxin-induced acute lung injury in rats / 中华麻醉学杂志

Objective To evaluate the role of endogenous heme oxygenase-1/carbon monoxide ( HO-1/CO) signaling pathway in endoplasmic reticulum stress during endotoxin-induced acute lung injury ( ALI) in rats. Methods Forty healthy clean-grade male Sprague-Dawley rats, aged 8 weeks, weighing 190-210 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), ALI group, ALI plus ZnPP-IX group (group AZ), and ALI plus vehicle sodium bicarbonate group ( group AV) . ALI was induced by intravenously injecting lipopolysaccharide 5 mg/kg in anesthetized rats. At 30 min before establishing the model, ZnPP-IX 10μmol/kg (diluted to 1 ml in 50 mmol/L sodium bicarbonate) was intraperitoneally injected in group AZ, and 50 mmol/L sodium bicarbonate 1 ml was intra-peritoneally injected in group AV. After injecting lipopolysaccharide for 6 h, blood samples were collected from the common carotid artery for determination of plasma CO concentration, the rats were then sacrificed, and lungs were removed for microscopic examination of the pathological changes which were scored and for determination of CO level, wet to dry weight ratio ( W/D ratio) , cell apoptosis ( by TUNEL) , and expres-sion of heme oxygenase-1 ( HO-1) , glucose-regulated protein 78 ( GRP78) , phosphorylated protein kinase R-like endoplasmie reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2 alpha ( p-elF2 ) , CCAAT/enhancer-binding protein homologous protein ( CHOP ) and caspase-12 in lung tissues ( by Western blot) . Apoptosis index ( AI) was calculated. Results Compared with group C, the lung injury scores, W/D ratio, AI and CO levels in plasma and lung tissues were significantly increased, and the expression of HO-1, GRP78, p-PERK, p-elF2, CHOP and caspase-12 was up-regulated in the other three groups ( P＜0. 05) . Compared with group ALI, lung injury scores, W/D ratio and AI were sig-nificantly increased, CO levels in plasma and lung tissues were decreased, the expression of HO-1 was down-regulated, and the expression of GRP78, p-PERK, p-elF2, CHOP and caspase-12 was up-regula-ted in group AZ (P＜0. 05), and no significant change was found in the parameters mentioned above in group AV ( P＞0. 05) . Conclusion HO-1/CO signaling pathway produces endogenous protection possibly through inhibiting endoplasmic reticulum stress during endotoxin-induced ALI in rats.

Effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury / 中华麻醉学杂志

Objective@#To evaluate the effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury (ALI).@*Methods@#Thirty clean-grade healthy adult male C57BL/6 mice, weighing 20-25 g, aged 2 months, were divided into 3 groups (n=10 each) using a random number table method: control group (group C), endotoxin-induced ALI group (group LPS) and endotoxin-induced ALI plus dexmedetomidine group (group LPS+ DEX). In LPS and LPS+ DEX groups, lipopolysaccharide (LPS) 10 mg/kg was injected via the caudal vein to establish the model of endotoxin-induced ALI.In group LPS+ DEX, dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before injection of LPS, while the equal volume of normal saline was given instead in C and LPS groups.The mice were sacrificed at 6 h after LPS administration, and lung tissues were obtained for examination of the pathological changes (with a light microscope) which were scored and for determination of the level of reactive oxygen species (ROS) and expression of mitochondrial fusion proteins mitofusin 1 (Mfn1), Mfn2, optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1) and fission protein 1 (Fis1)(using Western blot).@*Results@#Compared with group C, the lung injury scores and ROS level in lung tissues were significantly increased, the expression of Mfn1, Mfn2 and OPA1 was down-regulated, and the expression of Drp1 and Fis1 was up-regulated in LPS and LPS+ DEX groups (P<0.05). Compared with group LPS, the lung injury scores and ROS level in lung tissues were significantly decreased, the expression of Mfn1, Mfn2 and OPA1 was up-regulated, and the expression of Drp1 and Fis1 was down-regulated in group LPS+ DEX (P<0.05).@*Conclusion@#Dexmedetomidine can reduce endotoxin-induced ALI through maintaining the mitochondrial fusion-fission balance in mice.

In vitro study of histocompatibility and clearance of hemoperfusion adsorbents / 中华劳动卫生职业病杂志

Objective@#To evaluate the histocompatibility and clearance of chlorpyrifos and its metabolite of activated charcoal and adsorption resin by in vitro study.@*Methods@#Venous blood from volunteers were incubation with activated charcoal or adsorbent resins, cytometry parameters and plasma components were detected for evaluation the histocompatibility of adsorbents. Venous blood from volunteers mixed with chlorpyrifos and its metabolite were incubation with activated charcoal or adsorbent resins, plasma concentration of chlorpyrifos and its metabolite were detected for evaluation the efficacy of adsorbents.@*Results@#Incubation tests show that the absorbents reduce the blood platelet (F=3.671, P<0.05) , serum glucose (F=10.564, P<0.05) , albumin (F=5.239, P<0.05) , uric acid (F=7.175, P<0.05) , creatinine (F=23.673, P<0.05) , T3 (F=11.161, P<0.05) and free T3 (F=10.256, P<0.05) . However, other cytometry parameters and plasma components were not influenced. Both activated charcoal and adsorbent resins could reduce the plasma concentration of chlorpyrifos (F=798.110, P<0.01) and its metabolite (F=1495.212, P<0.05) .@*Conclusion@#In vitro test show that both activated charcoal and adsorbent resins could clear chlorpyrifos and its metabolite, however, could not influence main cytometry parameters and plasma components, the histocompatibility of adsorbents are satisfactory.

Novel Prognostic Nomograms for Hepatocellular Carcinoma Patients with Microvascular Invasion: Experience from a Single Center

BACKGROUND/AIMS: Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking. METHODS: A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models. RESULTS: The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson's capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p<0.001) and 0.698 (95% CI, 0.657 to 0.739; p<0.001), respectively, in the training cohort and 0.704 (95% CI, 0.650 to 0.708; p<0.001) and 0.673 (95% CI, 0.607 to 0.739; p<0.001), respectively, in the validation cohort. The calibration curves showed optimal agreement between the predicted and observed survival rates. The Kaplan-Meier curves suggested that these two nomograms had satisfactory discriminatory abilities. CONCLUSIONS: These novel predictive models have satisfactory accuracy and discriminatory abilities in predicting the prognosis of HCC patients with MVI after hepatectomy.

Effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury (ALI).Methods Thirty clean-grade healthy adult male C57BL/6 mice,weighing 20-25 g,aged 2 months,were divided into 3 groups (n=10 each) using a random number table method:control group (group C),endotoxin-induced ALI group (group LPS) and endotoxin-induced ALI plus dexmedetomidine group (group LPS+DEX).In LPS and LPS+DEX groups,lipopolysaccharide (LPS) 10 mg/kg was injected via the caudal vein to establish the model of endotoxin-induced ALI.In group LPS+DEX,dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before injection of LPS,while the equal volume of normal saline was given instead in C and LPS groups.The mice were sacrificed at 6 h after LPS administration,and lung tissues were obtained for examination of the pathological changes (with a light microscope) which were scored and for determination of the level of reactive oxygen species (ROS) and expression of mitochondrial fusion proteins mitofusin 1 (Mfn1),Mfn2,optic atrophy 1 (OPA1),dynamin-related protein 1 (Drp1) and fission protein 1 (Fis1) (using Western blot).Results Compared with group C,the lung injury scores and ROS level in lung tissues were significantly increased,the expression of Mfn1,Mfn2 and OPA1 was down-regulated,and the expression of Drp1 and Fis1 was up-regulated in LPS and LPS+DEX groups (P＜0.05).Compared with group LPS,the lung injury scores and ROS level in lung tissues were significantly decreased,the expression of Mfn1,Mfn2 and OPA1 was up-regulated,and the expression of Drp1 and Fis1 was down-regulated in group LPS+DEX (P＜ 0.05).Conclusion Dexmedetomidine can reduce endotoxin-induced ALI through maintaining the mitochondrial fusion-fission balance in mice.

Comparison of simeprevir versus telaprevir plus pegylated interferon alfa and ribavirin in patients with hepatitis C virus genotype 1 infection——a meta-analysis / 中华传染病杂志

Objective To compare the efficacy and safety of simeprevir-based (SMV) or telaprevir-based (TVR) triple therapy [SMV + Pegylated interferon alfa (PegIFNα) and ribavirin (RBV) versus TVR + PegIFNαand RBV] in patients with hepatitis C virus (HCV) genotype 1 infection .Methods A systematic literature searching was conducted in multiple online databases to identify relevant studies .The sustained virologic response rate at 12 (SVR12) and 24 weeks (SVR24) after end of the treatment were used as the efficacy endpoints .The rate of treatment related adverse events (AEs) ,discontinuation due to AEs and overall treatment discontinuation were used as safety endpoints . Patients were divided into multiple subgroups according to the previous treatment history to further compare the efficacy of the two treatment regimen .Statistical analyses were performed using the RevMan 5 .3 software .The Jajad score scale and the Newcastle-Ottawa scale were employed to evaluate the quality of included studies .Results A total of 5 clinical studies including 1666 HCV genotype 1 patients were included in this study .The pooled results showed that SVR12 rates in SMV group and TVR group were 67 .6％ and 68 .3％ , respectively .There was no significant difference in overall SVR12 rate between SMV and TVR groups (OR=0 .95 ,95％ CI:0 .76 -1 .18 , P=0 .65) .There was no significant heterogeneity among studies (P=0 .84 ,I2 = 0％ ) .For SVR24 rate ,the average SVR24 rate in SMV group was 78％ ,which was lower than that in TVR group of 84％ .However ,there was no significant difference in overall SVR24 rate between SMV and TVR groups (OR=0 .71 ,95％ CI:0 .42-1 .20 ,P=0 .20) .Meanwhile ,there was no significant heterogeneity among studies (P= 0 .69 ,I2 = 0％ ) .The subgroup analysis also showed that there was no significant difference in efficacy between SMV and TVR-based triple therapy for treatment-native patients ,prior partial response ,relapse ,and prior null response patients (all P>0 .05) .However , the pooled analysis indicated that both SMV-based and TVR-based triple therapies were most effective for the treatment-naive patients(SMV :85 .7％ ,TVR :85 .6％ ) .For the safety endpoints ,the incidence rate of anemia was significant lower in SMV group compared to TVR group (OR=0 .30 ,P<0 .001) .For the rate of overall treatment discontinuation ,there was no statistically significant difference between SMV and TVR group (OR=0 .48 ,P=0 .12) .Conclusions This meta-analysis suggests that the efficacy of SMV-based triple therapy is non-inferior to TVR-based triple therapy .However ,the SMV-based triple therapy is more tolerable and has a lower incident rate of anemia and discontinuation due to AEs compared to TVR-based triple therapy .

Effect of family factors on the prognosis of patients with epilepsy / 中华神经科杂志

Objective To investigate the effect of family factors on the prognosis of patients with epilepsy and the relationship between family factors and clinical characteristics of epilepsy.Methods Data were collected from 107 patients definitely diagnosed with epilepsy who were treated by antiepileptic drugs for at least two years.All the patients were divided into good or poor prognosis group according to whether achieving at least one year free of seizures.The clinical and family data were colleeted.The questionnaire Family Adaptability and Cohesion Evaluation Scale-Ⅱ-Chinese Version containing 30 items was used for patients and the Epilepsy Knowledge Questionnaire containing 34 questions for primary caregiver.We compared the clinical and family factors between the two groups to identify the predictors of poor control of seizures with univariate and multiple Logistic regression,and observed the relationship between family factors and clinical features such as course,type of seizure,seizure frequency,etc,with Pearson correlation analysis.Results Patients with poor prognosis were more likely to have interictal epileptiform discharges (IEDs),multidrug treatment and pre-treatment seizure frequency of more than once monthly (84.6％ (44/52) vs 50.9 ％ (28/55),x2 =13.797,P =0.000;63.5 ％ (33/52) vs 34.5 ％ (19/55),x2 =8.947,P =0.003;38.5％ (20/52) vs 5.5％ (3/55),x2 =17.257,P =0.000).Family in rural area,unbalanced family type,number of family members were much more in poor prognosis group than in good prognosis group (51.9％ (27/52) vs 25.5 ％ (14/55),x2 =7.923,P =0.005;80.8 ％ (42/52) vs 49.1％ (27/55),x2 =11.712,P=0.000;4.1 ± 1.1 vs 3.6 ±0.8,t=2.631,P=0.010).And average family income,education level of father,the level of epilepsy knowledge of primary caregiver were significantly lower in poor prognosis group than in good prognosis group (19/20/13 vs 11/17/27,x2 =7.198,P =0.027;15/30/7 vs 4/34/17,x2 =10.709,P =0.005;36/11/5 vs 15/25/15,x2 =19.022,P =0.000).Multiple Logistic regression analysis demonstrated that IEDs (OR =12.332,95％ CI 2.756-55.190,P =0.001),pretreatment seizure frequency of more than once monthly (OR =8.401,95％ CI 1.573-44.884,P =0.013)were clinical risk factors of unfavorable prognosis;more family members (OR =3.021,95％ CI 1.554-5.870,P =0.001),poor epilepsy knowledge of primary caregiver (OR =3.392,95％ CI 1.304-8.821,P=0.012) and unbalanced family type (OR=4.794,95％ CI 1.217-18.894,P=0.025) were independent family risk factors of poor prognosis.The level of epilepsy knowledge of primary caregiver was inversely associated with duration (r =-0.237,P =0.014).Conclusions The prognosis of epilepsy is not only affected by clinical factors,but also by family factors.More family members,poor epilepsy knowledge of primary caregiver and unbalanced family type are independent risk factors of unfavorable prognosis.The poorer epilepsy knowledge the primary caregivers have,the longer duration the disease has.