Volume 100 ·  Issue 12 ·  2020

Patients with severe burn trauma are often complicated by sepsis, and further development can lead to multiple organ dysfunction syndrome (MODS). In 2016, sepsis was redefined as life-threatening organ dysfunction caused by the body's dysresponse to infection. The pathogenesis of sepsis is complex, involving systemic multi-system dysfunction, such as uncontrolled inflammatory response, immune dysfunction, coagulation dysfunction, neuroendocrine-immune system dysfunction, etc. There are many involved factors and influence each other, forming a complex nonlinear network effect. On the basis of deep analysis of the pathogenesis of sepsis, multi-factor intervention is the future direction of sepsis treatment.

The further development of precision medicine and the establishment of new medical models will change the existing doctor-patient relationship. While weakening the authority of doctors and challenging their "gatekeeper" position, they will put patients in a new weak position. Different from the traditional weak position of patients caused by the unequal power of doctors and patients, the new weak position of patients is the digitization of all health information under the new medical model, the widespread use of quantitative biomarkers, and the precision medicine under the PPP model. The mixed nature of companies and other factors contribute to it.

As the fight against novel coronavirus pneumonia (COVID-19 for short) enters the critical stage, many critically ill patients have appeared clinically, and nutritional therapy has become one of the important means for these critically ill patients to tide over the difficulties. In order to improve the treatment effect of severe patients in COVID-19, the Parenteral and Enteral Nutrition Branch of Chinese Medical Association organized experts to formulate this recommendation.

To investigate the effect of Silent information regulator 1 (Sirt1) on the expression profile of long non-coding RNA (lncRNA) in macrophages upon lipopolysaccharide (LPS) treatment.

Peritoneal macrophages (PM) were isolated from nine wild-type C57BL/6 male mice (wild-type group) and nine myeloid-specific Sirt1 knock-out mice (knock-out group). RNA samples were extracted from macrophages stimulated with 1 μg/ml LPS. Sequencing and the differentially expressed lncRNA were screened after the RNA was quantified. The threshold set for up-and down-regulated genes was a fold change (wild-type group/knock-out group) ≥2 and P≤0.05. Afterwards, gene ontology (GO) and pathway enrichment analysis were conducted and co-expression network map was constructed.

Four hundred and forty five lncRNA genes were differentially expressed (185 lncRNA genes were up-regulated and 260 lncRNA genes were down-regulated). Two hundred mRNA genes were differentially expressed (113 mRNA genes were up-regulated and 87 mRNA genes were down-regulated). It was found that the differentially expressed lncRNA genes and the predicted corresponding target genes were mainly distributed in the regions of biological processes of macrophage inflammatory response, macrophage chemotaxis and cell metabolism by GO and pathway enrichment analysis.

lncRNA expression profile changes significantly in LPS induced macrophages isolated from Sirt1 knock out mice, which is closely related to the function of macrophages.

To investigate the effect of long non-coding RNA-AC013472.3 on lipopolysaccharide (LPS)-stimulated secretion of tumor necrosis factor (TNF)-α in NR8383 rat alveolar macrophages.

Silencing and overexpression models of lncRNA-AC013472.3 were established with NR8383 rat alveolar macrophages as the experimental subjects. The silencing models were divided into three groups: random nonsense negative small interfering RNA sequence (si-con) group (si-con group, si-con transfected NR8383 cells), LPS+si-con group (10 μg/L LPS was used to treat si-con transfected NR8383 cells for 24 h), and siRNA group (siRNA transfected NR8383 cells), and LPS+siRNA group (10 μg/L LPS was used to treat siRNA transfected NR8383 cells for 24 h). The overexpression models were divided into the empty plasmid (p-con) group (p-con transfected NR8383 cells), LPS+p-con group (10 μg/L LPS was used to treat p-con transfected NR8383 cells for 24 h), lncRNA overexpression plasmid (plncRNA) group (plncRNA transfected NR8383 cells), and the LPS+plncRNA group (10 μg/L LPS was used to treat plncRNA transfected NR8383 cells for 24 h). The mRNA levels of TNF-α in each group were examined by quantitative real-time PCR (qPCR). The protein levels of tumor necrosis factor receptor-related factor-6 (TRAF-6) and phosphorylated nuclear factor-κB (NF-κB) p65 were examined by Western blot.

In the silencing model, the mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+si-con group were significantly higher than those in the si-con group (2.040±0.195 vs 1.048±0.207, 0.473±0.022 vs 0.293±0.076 and 0.469±0.062 vs 0.252±0.038)(allP<0.05). The mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+siRNA group were significantly higher than those in the siRNA group (4.158±0.119 vs 1.028±0.019, 0.700±0.104 vs 0.231±0.023 and 0.771±0.095 vs 0.258±0.050)(allP<0.05). The relative expression levels of all indexes in the LPS+siRNA group were significantly higher than those in the LPS+si-con group (all P<0.05). In the overexpression model, the mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+p-con group were significantly higher than those in the p-con group (1.961±0.169 vs 0.999±0.143, 0.533±0.047 vs 0.247±0.020 and 0.565±0.108 vs 0.276±0.048) (allP<0.05). The mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+plncRNA group were significantly higher than those in the plncRNA group (1.322±0.110 vs 1.043±0.093, 0.347±0.035 vs 0.232±0.023 and 0.405±0.072 vs 0.268±0.031) (allP<0.05). The relative expression of all indexes in the LPS+plncRNA group were significantly lower than that in the LPS+p-con group (all P<0.05).

LncRNA-AC013472.3 may inhibit the activation of NF-κB signaling pathway, thereby inhibiting the LPS-stimulated secretion of TNF-α in NR8383 rat alveolar macrophages.

To explore the mechanism of CD38-mediated cardiac damage under hypoxic-ischemic (H/I) conditions.

Twenty CD38^-/- male mice (8-week-old) and 20 wild-type (WT) male C57BL/6J mice (8-week-old) were randomly selected to construct the model of approximately 25% of the total body surface area (TBSA) burn injury. The cardiomyocytes (CMs) were separated from neonatal mice (1day) to construct the H/I injury model. Ad-CD38 adenovirus was transfected into CD38^-/- primary CMs to callback CD38 expression. Animal experiments were grouped into WT-control group, CD38^-/--control group, WT-burn group, and CD38^-/--burn group (10 mice in each group). Primary CMs were divided into 6 groups: WT-normoxia group, CD38^-/--normoxia group, CD38^-/-+Ad-CD38-normoxia group, WT-H/I group, CD38^-/--H/I group, CD38^-/-+Ad-CD38-H/I group. The release of lactic dehydrogenase (LDH) from CMs and the cell viability were measured to estimate the level of myocardial injury. Ultrastructure of cardiomyocytes was examined by electron microscope. CD38 protein level and mitochondrial apoptosis-related proteins were detected by Western blot. Flow cytometry was used to detect mitochondrial reactive oxygen species (MitoSOX) of CMs under H/I condition. Cardiac function of mice was detected by ultrasonic apparatus.

(1) Animal experiments: The expression level of cardiac CD38 in WT-burn group was significantly higher than that in sham group (P<0.001). The heart function of CD38^-/--burn group was obviously better than WT-burn group [ejection fraction (EF)%: (84.70±2.31)% vs (76.10±2.96)%, shortening fraction (FS)%: (48.90±5.00)% vs (38.10±2.80)%] (both P<0.001). (2) Cell experiments: The expression level of cardiac CD38 in WT CMs under H/I condition was significantly higher than that in WT CMs under normoxia condition (P<0.05). The level of LDH, apoptotic cell and MitoSOX in CD38^-/--H/I group were fewer than WT-H/I group and CD38^-/-+Ad-CD38^-H/I group [(11.2±3.0)% vs (18.2±3.4)% and (17.6±4.0)%, (13.0±2.8)% vs (23.1±4.9)% and (23.3±6.0)%, (162±11)% vs (228±18)% and (220±18)%] (all P<0.001). The levels of cleaved-caspase3, Cytochrome-C in CD38^-/--H/I group were significantly lower than those in WT-H/I group and CD38^-/-+Ad-CD38-H/I group (P<0.001). The cell viability in CD38^-/--H/I group was higher than that in WT-H/I group and CD38^-/-+Ad-CD38-H/I group (0.355±0.043 vs 0.280±0.051 and 0.291±0.024) (all P<0.05). Electron microscopy results showed that structure of mitochondria in CD38^-/--H/I group was better than in WT-H/I group and CD38^-/-+Ad-CD38-H/I group.

Overexpression of CD38 contributes to cardiac damage by stimulating mitochondrial apoptotic pathway.

To explore the effect and potential mechanism of cardiac adipose triglyceride lipase (ATGL) overexpression on burn-induced cardiac injury.

Eight-week-old C57BL/6J mice with cardiac ATGL overexpression driven by the myosin heavy chain (MHC) promoter (MHC-ATGL burn group) and wild-type (wild-type burn group) mice were randomly chose to the following experiments with burn injury after 24 h (n=8/group), MHC-ATGL mice and wild-type mice with corresponded age and sex were included as control. Cardiac ATGL protein expression, serum levels of cardiac troponin T and cardiac kinase-MB (CK-MB), cardiac free fatty acid and reactive oxygen species were detected. The wild-type and MHC-ATGL burn groups were not only compared with their corresponded control groups, but also compared between each other.

The hair color and development were shown little difference between each group. ATGL protein expression is elevated in wild-type burn group (1.00±0.68 vs 3.09±0.93, P=0.023) and decreased in MHC-ATGL burn group (17.84±2.41 vs 10.36±2.22, P<0.001), while ATGL protein expression is still increased in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Serum levels of cardiac troponin T and CK-MB were both elevated in wild-type burn group and MHC-ATGL burn group [(0.456±0.131) vs (0.076±0.019) μg/L and (0.219±0.089) vs (0.060±0.019) μg/L, (1 421±162) vs (221±67) U/L and (761±142) vs (221±41) U/L] (all P<0.001), while serum levels of cardiac troponin T and CK-MB was still decreased in MHC-ATGL burn group compared with wild-type burn group (P<0.001). In addition, cardiac free fatty acid was increased in wild-type burn group and little difference was found in MHC-ATGL burn group [(2.54±0.51) vs (0.46±0.27) mmol/L, P<0.001, and (0.81±0.38) vs (0.59±0.25) mmol/L, P=0.251], while cardiac free fatty acid was significant reduction in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Levels of cardiac reactive oxygen species was both elevated in wild-type burn group and MHC-ATGL burn group [(1.89±0.23) vs (1.00±0.18) and (1.38±0.17) vs (0.95±0.13)] (both P<0.001), while levels of cardiac reactive oxygen was reduction in MHC-ATGL burn group compared with wild-type burn group (P<0.001).

Cardiac ATGL overexpression may protect against burn-induced cardiac injury through reducing free fatty acid and reactive oxygen species production.

To summarize the etiology of primary adrenal insufficiency (PAI) and analyze its clinical features.

A retrospective analysis was performed in the Department of Endocrinology, Peking Union Medical College Hospital from October 1981 to June 2019. Patients with PAI as the first symptom were enrolled. The etiology of PAI was analyzed and the clinical characteristics was also summarized.

A total of 131 patients with PAI were enrolled, including 87 males and 44 females (57 adolescents, and 74 adults). The age ranged from 0 to 73 years. The primary cause of PAI in adolescents was genetic defects (52.6%, 30/57), in which congenital adrenal dysplasia caused by DAX1 gene deficiency accounted for 50.0% (15/30), followed by autoimmunity (22.8%, 13/57). The primary cause of adult PAI was infection (58.1%, 43/74), of which tuberculosis accounted for the majority (93.0%, 40/43), and autoimmune adrenalitis accounted for 19.0% (14/74). Compared with the tuberculosis group, female patients were more common, and the onset age was younger, the plasma cortisol, serum sodium, fasting blood glucose, creatinine and aldosterone were lower (all P<0.05), and serum potassium and renin levels were higher in the autoimmune adrenalitis group (both P<0.05).

In the current study, the proportion of PAI caused by infection in the adult group was higher than that in the adolescent group. The most common cause of adult PAI was tuberculosis infection. The most common cause of childhood PAI was genetic defects. Autoimmune damage to the adrenal glands may be more severe than tuberculosis infection.

To compare postoperative short-term outcomes and long-term prognosis between perioperative Enhanced Recovery After Surgery (ERAS) and conventional pathways protocols in gastric cancer patients.

This is a single institute retrospective cohort study, all patients were pathologically proved to be gastric adenocarcinoma, underwent standard radical gastrectomy with D2 lymphadenectomy during the period of 2007-2012. Total 2124 cases were eligible to be analysed and divided into ERAS groups and Non-ERAS group according to the different perioperative pathway protocol. Propensity score matching method (in SPSS, 24.0 version, IBM Company) was used to balance the baseline characteristics. Two groups were matched in a 1∶1 ratio. There were 521 cases per group after matched. The short-term clinical outcomes (postoperative complications, length of hospital stay, blood loss, 30-day re-admission rate, etc.) and overall 5-year survival rates were compared between the two groups.

The incidence of overall postoperative complications was similar between the two groups (ERAS group=18.4%, non-ERAS group=19.4%, P=0.69), including anastomotic leakage, abdominal hemorrhage, etc. But the incidence of SSI, atelectasis, and thromboembolic disease in ERAS group was significant lower than that in Non-ERAS group. The number of lymph node harvested, operation time, intraoperative blood loss, postoperative hospital and cost in ERAS group were better than those in non-ERAS group. There were no significant differences in unplanned reoperation (ERAS group=3.1%, non-ERAS group=2.1%, P=0.33), 30 day readmission rate of discharge (ERAS group=6.1%, non-ERAS group=5.6%, P=0.69) and postoperative mortality (ERAS group=0.4%, non-ERAS group=0.2%, P=0.56) between the two groups. The 5-year overall survival rates of non-ERAS group and ERAS group were 66.2% and 72.8% respectively (P=0.007). The subgroup analysis found that 5-year OS rates of stage I were 93.4% and 92.7% (P=0.73), these of stage Ⅱ and Ⅲ were 82.2% vs 75.2% (P=0.007) and 47.6% vs 35.7% (P=0.02) in ERAS group and non-ERAS group respectively.

Perioperative ERAS pathway management is safe and feasible for patients with gastric cancer, without increasing the incidence of complications and 30-day readmission rate. This protocol can improve the prognosis of patients with gastric cancer.

To analyze the influencing factors of acute kidney injury (AKI) in patients after cardiac surgery using levosimendan or dobutamine, and explore the effect of positive inotropic drugs on AKI.

The clinical data of 417 patients undergoing cardiac surgery from January to June 2018 in Beijing Anzhen Hospital and treated with levosimendan or dobutamine during perioperative period were retrospectively reviewed and collected. Patients were divided into AKI group and non-AKI group according to whether AKI occurred. Univariate logistic regression analysis was used to analyze the factors related to the occurrence of AKI. The statistically significant factors (P<0.05) were further included in the multivariate logistic regression analysis.

Totally, 417 patients were enrolled in the study, with a mean age of (58.2±10.4) years old and a male rate of 65.0% (n=271), and the AKI incidence rate was 25.2% (105/417). Univariate logistic regression analysis showed that male, chronic kidney disease, high serum creatinine level in preoperative period, aortic obstruction time ≥ 120 minutes and extracorporeal circulation time ≥ 120 minutes were risk factors for AKI (all P<0.05). Vasodilator and levosimendan treatment during perioperative period were protective factors (P<0.05). Multivariate logistic regression analysis showed that chronic kidney disease (OR=17.291, 95%CI: 4.335-68.960, P<0.001) and high serum creatinine level (OR=1.097, 95%CI: 1.074-1.121, P<0.001) in preoperative period were independent risk factors for AKI. Perioperative application of levosimendan (OR=0.533, 95%CI: 0.288-0.984, P=0.044) was an independent protective factor.

Risk factors for AKI after cardiac surgery include chronic kidney disease and high serum creatinine level in preoperative period. The use of levosimendan during preoperative period has the potential effect to protect against AKI.

To investigate the relationship between gene mutation characteristics, mutation burden and general condition, disease subtype and karyotype of patients with myelodysplastic syndrome (MDS), and its clinical value.

High-throughput sequencing was used to detect 65 blood tumor-related genes in 191 MDS patients and 9 secondary acute myelocytic leukemia patitents(SAML), and to analyze the characteristics of abnormal genes, mutation burden, as well as the relationship with disease subtypes, chromosome karyotypes and age.

Mutations were found in 148 patients (77.5%), including 47 abnormal genes and 186 mutation sites. And gene mutations were found in 9 SAML patients, the number of mutations was significantly higher than that in MDS patients (χ²=11.911, P=0.018). Among the abnormal genes, the mutation frequency of U2AF1 (37.3%) and ASXL1 (41.6%) were higher, and there were significant differences in mutation burden among different abnormal genes (F=91.946, P<0.001). There were differences in the number of gene mutations among different subtypes of MDS, and the number of EB-2 gene mutations was the highest (2.2±1.5). In SLD, MLD, EB-1 and EB-2, the proportion of carrying ≥ 3 mutations increased gradually (χ²=52.471, P=0.037). TP53 mutation was associated with abnormal karyotype (r_φ=0.177, P=0.019), especially with complex karyotype (r_φ=0.440, P<0.001), while NPM1 mutation is associated with normal karyotype (r_φ=0.173, P=0.024). The number of mutations carried by patients under 30 years old was the least, and the number of mutations increased with the increase of age. The number of mutations was the most in patients aged 60 to 79 years old (P=0.017), and the mutation frequency of epigenetic related genes increased with the increase of age (P=0.041).

The mutation characteristics and mutation load of MDS-related genes are closely related to clinical factors such as disease subtype, chromosome karyotype and patient age.

The aim of present study is to analyze clinical and laboratory features of mixed connective tissue disease (MCTD)-associated trigeminal neuropathy (TN).

Clinical records of 12 cases of MCTD complicated with TN diagnosed in Peking University People′s Hospital from January 2008 to October 2019 were analyzed retrospectively.

The present study included 12 cases, 1 males and 11 females, average age was(40±13)years. TN was developed before the diagosis of MCTD in 1 case. TN and MCTD were occurred simutaneously in 1 case. Raynaud phenomenon (12 cases), arthritis (10cases), edema of fingers (9cases), myositis (6 cases), and pulmonary involvement (11cases) were main cinical feature of MCTD-associate TN. Antinuclear antibody (ANA) and high titer anti-U1-RNP antibody could be detected in serum of all patients. Elevated erythrocyte sedimentation rate (ESR) and creatine kinase were found in serum of 7cases and 5cases, respectively. Blink reflex tests were positive in 6 cases. Neurological symptoms improve slowly without any progress by using glucocorticoid combined immunosuppressants or intravenous gamma globulin.

TN is often associted with actived MCTD. Positive ANA and anti-U1-RNP antibody were common in MCTD-associated TN. Blink reflex test is essential to diagnose MCTD-associated TN. Intensive treatment of MCTD contributes to control the progress of TN.

The aim of this study was to investigate the effects of silencing Paired related homoeobox 2 (Prrx2) expression on the proliferation of breast cancer and its molecular mechanisms.

Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2. The level of Prrx2 was verified by Western blot. MTT assay was used to analyze the proliferation of breast cancer cells in vitro. To investigate the effect of Prrx2 depletion on tumor growth in vivo, a nude mouse xenograft model was performed.

The expression of Prrx2 decreased 91.2% in MDA-MB-231 cells and 88.7% in MCF-7 cells after transfection with interfering vectors (P<0.05). MTT assay showed that the proliferation of cells in silenced Prrx2 expression group was significantly inhibited compared with the control group (P<0.05). Nude mice transplanted tumors showed that the growth of transplanted tumors was slow after silencing Prrx2 expression, and the weight of the tumors of silenced Prrx2 expression group were smaller than those of the control group ((160.2±26.3)mg vs (365.4±19.7)mg, P<0.05). Western blot showed that silencing Prrx2 expression inhibited the expression of β-catenin in breast cancer cell nucleus and down-regulated the activity of Wnt/β-catenin signaling pathway.

Silencing Prrx2 expression can effectively inhibit the proliferation and growth of breast cancer, suggesting that Prrx2 may become a new target for the treatment of breast cancer.

The patient was an 18-year-old woman who was admitted to the hospital mainly for "primary amenorrhea, adrenal gland was found to occupy space for 1 month". The patient developed breast development at the age of 11 and pubic hair and axillary hair growth at the age of 13, but there were no menstrual cramps. The artificial cycle treatment given by other hospitals was ineffective; At the age of 16, my face became rounded and my hair increased. Auxiliary examination showed that blood progesterone, dehydroepiandrosterone sulfate, testosterone, and cortisol were increased, and adrenocorticotropic hormone was decreased. The inhibition test of medium-dose dexamethasone was not inhibited, and adrenal imaging examination showed that the left adrenal gland area occupied space. Considering the possibility of multifunctional endocrine adenoma of the adrenal gland, the left adrenal gland tumor was resected under general anesthesia, and the postoperative pathology showed adrenal cortical adenoma. After operation, the patient had loss of appetite, skin molting, menarche occurred 1 month after operation, and the levels of blood progesterone, dehydroepiandrosterone sulfate, testosterone and cortisol decreased after re-examination.

This paper reports a case of an elderly female patient with high fever onset and initial diagnosis considering urinary system infection combined with biliary system infection. After anti-infection treatment, the residual low fever and inflammatory indexes were significantly increased. After tracing the medical history, previous imaging examination and further improving PET-CT examination, it was finally diagnosed as giant cell arteritis combined with polymyalgia rheumatica. Because there are no typical clinical manifestations such as temporal headache and claudication, and there are no signs of vascular murmur, these patients are easily missed in clinic. New imaging techniques such as PET-CT have become an important method for the diagnosis of macrovascular disease, but the value of traditional imaging examination for macrovascular disease cannot be ignored.

Traumatic coagulopathy (TIC) is a coagulation dysfunction caused by endogenous factors in the early stage of trauma. It has the characteristics of complex pathological mechanism, diverse phenotypes, multi-factor involvement, time sensitivity and high risk of death. On the basis of traditional coagulation screening, the combination of viscoelastic coagulation test and blood transfusion score can facilitate early identification of TIC. There are still many gaps and inconsistencies in the research on the pathogenesis, detection technology, diagnostic criteria and predictive score of TIC. This paper introduces the relevant research progress as follows.

Preeclampsia is a syndrome caused by multiple factors, mechanisms and pathways^[1], often accompanied by injuries to different organs, is the main cause of maternal and neonatal death^[2]。 Preeclampsia-related liver impairment is the most common in liver impairment during pregnancy, and pro-angiogenic factors such as vascular endothelial growth factor (VEGF), placental growth factor (PLGF) and anti-angiogenic factors such as soluble vascular endothelial growth factor receptor (sFlt-1), soluble endothelial factor (sEng) system imbalance or placental angiogenesis imbalance are related to the occurrence and development of preeclampsia. There is growing evidence that sFlt-1, PLGF, and sEng are imbalanced in severe preeclampsia, including low platelet count (HELLP). The research on the relationship between vascular endotheliogenic factor and preeclampsia liver damage in recent years is reviewed as follows.