Volume 96  ·  Issue 38  ·  2016

In early 2015, US President Barack Obama officially announced the launch of the "Precision Medicine Program" in his State of the Union address. For a time, precision medicine quickly became a global health hot word and a new concept to promote the development of medicine. The so-called precision medicine is a new medical model characterized by individualized medicine and based on genome sequencing technology and bioinformation and big data analysis. The aim is to analyze, identify, verify and apply biomarkers to large sample populations and specific disease types by using omics technology and cutting-edge medical technology, so as to accurately find disease causes and therapeutic targets, and accurately classify diseases by subtypes, and finally realize personalized precision treatment for diseases and specific patients^[1,2]。

With the rapid growth of China's economy and the substantial improvement of national living standards, the public demand for high-quality medical services is also increasingly strong. Due to the two-way pressure of China's population and finance, the government's investment in the medical field is very limited, which leads to the serious shortage of the number of medical institutions and the supply of medical services, which objectively causes the situation of "difficult to see a doctor". In this round of public hospital reform, the drug addition that hospitals depend on for survival will be completely banned, the phenomenon of supporting doctors with medicines will no longer exist, and the development funds of hospitals will mainly come from government compensation. However, as China's economy enters a new normal, the downward pressure on the economy increases, and the financial operation becomes increasingly tense. Full compensation for public hospitals can only be a moon in the water and a flower in the mirror. In order to maintain the basic operation and development needs of hospitals, if public hospitals pass on the funding gap to patients, the phenomenon of "expensive medical treatment" will not only not be corrected, but will also become more and more severe; Or by changing ideas, bravely innovating, actively looking for other financial support channels. Since the reform and opening up, while the state-owned economic strength continues to grow, private enterprises have also completed the primitive accumulation, and have good financial strength and strong development momentum. However, a large amount of private capital in China is idle, and the public is eagerly looking forward to new investment fields. In this way, the mode of cooperation between government, social capital and Public hospitals (Public-Private Partnership, PPP mode) came into being. After the PPP model enters the practice of public hospitals, it will surely break the traditional operation mode of public hospitals, which may lead to a series of problems such as property rights changes and loss of state-owned assets. Therefore, this paper will explore the possible problems from the property right system reform, state-owned assets protection and human resources construction, and put forward corresponding legal countermeasures to ensure the smooth implementation of PPP mode in the application of public hospital projects.

To detect the expression of heparanase (HPSE) in oral squamous cell carcinoma (OSCC) with different metastatic potentials and investigate its clinical significance.

Transcriptional and translational status of HPSE in OSCC cell lines with different metastatic capacities, primary OSCC samples and their paired metastatic cancer tissues were determined using real-time polymerase chain reaction (PCR) and Western blotting analysis. Immunohistochemistry was used to evaluate HPSE expression in 131 OSCC samples. The correlation between HPSE expression pattern and clinicopathological parameters and clinical outcome in patients with OSCC were analyzed. HPSE level was reduced using HPSE-siRNAs in OSCC cell lines and its impact on cell migration and invasion was measured by scratch assay and matrigel invasion assay.

The mRNA and protein levels of HPSE were remarkably up-regulated in OSCC cell lines with highly metastatic capacity (P<0.000 1) and metastatic OSCC tissues (P<0.000 1). The protein levels of HPSE were strongly associated with lymph node metastasis (P<0.000 1) and tumor node metastasis stage (P=0.012). Survival analyses revealed that high HPSE expression was associated with worse overall survival (P=0.000 3). Multivariate Cox proportional analyses indicated that HPSE expression was strongly associated with clinical outcome in patients with OSCC (HR=2.203, 95% CI: 1.203-3.988, P=0.009). The siRNA-mediated silencing of HPSE could suppress the migration and invasion (P=0.008) of HN12 cells in vitro.

The up-regulation of HPSE contributes to invasion and metastasis of OSCC. HPSE may serve as a useful biomarker for patients with OSCC.

To investigate the efficacy and the influence factors of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma (mRCC).

Clinical data of mRCC patients with sunitinib administered as the first line treatment from August 2008 to December 2015 were retrospectively reviewed. The efficacy and the influence factors of sunitinib treatment was analyzed using the Kaplan-Meier method and Cox proportional hazards models.

In all 166 patients who received sunitinib as first-line treatment, objective response rate was 31.9%, disease control rate was 84.3%. The median progression free survival (PFS) and overall survival (OS) were 11.0 months (95% CI: 9.0-14.0) and 28.0 months (95% CI: 19.0-33.0), respectively. Multivariate analysis showed that pathological types (clear cell carcinoma vs non clear cell carcinoma, HR: 1.889 vs 2.353), time from diagnosis to treatment(<1 year vs ≥1 year,HR: 0.293 vs 0.322) and the number of metastatic sites (1 vs ≥1, HR: 2.360 vs 4.351) were the independent prognostic factors for PFS and OS (P<0.05).

The efficacy of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma is similar to reports at home and abroad. The patients with renal clear cell carcinoma, time from diagnosis to treatment> 1 year, and only one metastatic site would get better PFS and OS.

To examine the clinical features of patients with acute respiratory failure (ARF) caused by pneumocystis pneumonia (PCP) admitted into two medical intensive care units (ICU) in non- human immunodeficiency virus (HIV) infected immunocompromised patients.

A retrospective review was conducted among 92 non-HIV patients with ARF caused by PCP in medical ICU of Peking Union Medical College Hospital and China-Japan Friendship Hospital between Jan 2010 and Dec 2015. Patient characteristics, clinical presentation, laboratory and radiological findings, complications, as well as therapy and mortality were included in the analysis.

All patients were immunocompromised before PCP, among which 69.6% (64/92) patients were suffered from autoimmune disease. The diagnosis of PCP was made by the identification of P. jiroveci organisms with Giemsa or polymerase chain reaction in specimens of bronchoalveolar lavage, sputum or tracheal aspiration. The Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ was high (19±5) and the partial pressure of oxygen/ fraction of inspiration oxygen(PaO₂/FiO₂) ratio was low[(139.6±65.4) mmHg]on ICU admission, with all patients diagnosed as acute respiratory failure during ICU stay. Radiologic findings showed bilateral diffused ground glass opacity (94.6%, 87/92). All patients received Compound Sulfamethoxazole (SMZ/TMP) and only 3.3% (3/92) patients were not given conjunctive corticosteroid. 57.6% (53/92) and 21.7% (20/92) patients were coinfected by cytomegalovirus (CMV) and aspergillos. Invasive ventilatory support was required in 90% (81/90) patients. 22% (18/82) patients used non-invasive positive pressure ventilation (NPPV) on ICU admission but most of them (83.3%, 15/18) failed and switched to invasive positive pressure ventilation (IPPV). Median ICU and hospital length of stay were 11 and 17 days, respectively. The overall hospital mortality rate was 76.1% (70/92).

Among patients with ARF secondary to non-HIV related PCP, autoimmune system diseases are the most common primary diagnosis. The clinical manifestations were severe and coinfections are common, with poor prognosis.

To investigate the effect of 50 mg alteplase to intermediate-risk acute pulmonary embolism (APE) with right ventricular dysfunction.

From May 2011 to May 2015, a total of 73 patients with intermediate-risk APE, furthermore, right ventricular systolic pressure (RVSP)>40 mmHg and B-type natriuretic peptide (BNP)>100 ng/L, were allocated to receive 50 mg alteplase plus anti-coagulation (thrombolysis group, TG,n=35) or anticoagulation alone (control group CG, n=38) according to their will.Tricuspid annular plane systolic excursion (TAPSE), Right ventricular fractional area change (RVFAC), RVSP, BNP, CT obstruction index (CTOI) were detected at prior treatment, 1^st day, 14^th day, 3^rd month, 6^th month. The adverse events consisting of hemodynamic decompensation (within 14 days), mortality, bleeding, recurrent pulmonary embolism (PE), RVSP>40 mmHg (at 6^th month) were recorded.

At prior treatment, TAPSE, RVFAC, RVSP, BNP and CTOI between TG and CG were (10.9±1.4) vs (11.4±1.2) mm, (27.8±3.9)% vs (28.1±4.1)%, (55.6±7.9) vs (54.6±8.4) mmHg, (491±76) vs (482±71) ng/L and (23.4±4.2)% vs (23.7±4.5)%. There was not statistical difference between two groups (all P>0.05). From 1^st to 14^th day, these indexes had better and faster improvement in TG than CG. At 6^th month, TAPSE, RVFAC, RVSP and CTOI between two groups were (17.5±1.3) vs (15.4±1.1) mm, (49.4±3.9)% vs (46.0±2.8)%, (15.8±2.2) vs (17.8±4.2) mmHg, and (1.7±1.6)% vs (4.0±3.0)% (all P<0.05), BNP was (66±13) vs (71±15) ng/L (P>0.05). From prior treatment to 6^th month, the tendency of variation of these index in TG was better than CG (P<0.05). From prior treatment to 14^th day, 3 cases of hemodynamic decompensation occurred in CG, 0 case in TG.During treatment, there were not cases of death and major bleeding. At 6^th month, there were 4 cases of RVSP>40 mmHg in CG, while 0 case in TG (P=0.048).

50 mg alteplase can reduce the thrombus in pulmonary artery, improve right ventricular function quickly, and decrease the risk of elevated RVSP in the long term, for the patients with intermediate-risk APE.

To investigate the value of the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing mediastinal enlarged lymph nodes.

A total of 210 patients with mediastinal enlarged lymph nodes from the First Affiliated Hospital of Zhengzhou University from 2014 July to 2015 October were enrolled for EBUS-TBNA. Endobronchial ultrasound (EBUS) imaging features, including lymph node short diameter, the ratio of longitudinal to transverse diameter, the blood flow and morphology destroy, in benign and malignant lymph nodes were evaluated separately and their relationships with the rate of malignant lymph nodes were also analyzed. The significant variables according to single factor analysis were brought into the Logistic multivariate analysis, which investigated the risk factors of malignant lymph nodes. The best cut-off point of the short diameter of lymph nodes was analyzed by receiver operating characteristic curve (ROC). The sensitivity, specificity and accuracy of EBUS-TBNA in the diagnosis of malignant lymph nodes were analyzed by the standard calculation formula.

The sensitivity, specificity, accuracy rate of EBUS-TBNA diagnosing lung cancer and other tumor with mediastinal lymph node metastasis were 91.2%, 100%, 93.8%. The rates of malignant in lymph node with short diameter ≥1.0 cm, ratio of longitudinal to transverse diameter<1.5, blood flow distribution Ⅱ-Ⅲ, morphology destroy by the EBUS measurement were higher than those in the lymph node with short diameter<1.0 cm, ratio of longitudinal to transverse diameter ≥ 1.5, the blood flow distribution 0-Ⅰ, without morphology destroy (79.8%, 77.8%, 84.7%, 76.7% vs 37.7%, 44.6%, 42.9%, 42.9%), and the four factors were independent risk factors for malignant lymph nodes (allP<0.001). The ROC curve indicated the optimal cut-off point of short diameter was 8.2 mm. The accuracy of diagnosis by the combination of the above 4 ultrasound features, those were the lymph node short diameter not less than 1 cm, the ratio of longitudinal to transverse diameter less than 1.5, the blood flow distribution Ⅱ-Ⅲ and morphology destroy, was higher than those of the single factor (89.3% vs 74.7%, 67.9%, 67.8%, 67.5%) (allP<0.001).

EBUS-TBNA has satisfying value in diagnosing malignant mediastinal enlarged lymph nodes.

To investigate the effect of Berberine on renal tubulointerstitial injury and its potential mechanism in rats with type 2 diabetes mellitus (T2DM).

Thirty Sprague-Dawley rats were randomly divided into 3 groups: normal control rats (NC group), diabetic rats without drug treatment (DM group), diabetic rats treated with Berberine (BBR group) for 8 weeks. At the end of the study, blood and urine samples were collected for biochemical examination, and tubulointerstitial fibrosis was quantified by Hematoxylin and Eosin (HE) and Masson staining. The expressions of E-cadherin (E-cad), α-smooth muscle actin (α-SMA), nuclear factor-κB (NF-κB) and monocyte chemoattractant protein 1 (MCP-1) were detected by immunohistochemistry analysis, real-time polymerase chain reaction (RT-PCR) and Western blot analysis.

24 h urinary microalbumin (mAlb)[(170.5±58.1) vs (253.7±53.0) mg]and urinary N-acetyl-glucosaminidase (NAG)[(33.5±7.2) vs (49.5±9.3)U/L]in diabetic rats were significantly decreased by BBR treatment(bothP<0.05). The apparent renal tubulointerstitial injury was found in the DM group, which was ameliorated by BBR treatment. The expression of α-SMA, NF-κB and MCP-1 were significantly decreased, accompanied by increased expression of E-cad in BBR-treated DM rats (allP<0.05).

BBR could ameliorate renal tubulointerstitial injury in diabetic rats, the mechanism of which may be associated with the amelioration of epithelial-mesenchymal transition (EMT) through suppressing the expression of the NF-κB and MCP-1.

To study the role of human antigen R (HuR) regulated transforming growth factor β ₁ (TGF-β₁) expression in airway smooth muscle cells under the stimulation of platelet-derived growth factor (PDGF).

Airway smooth muscle (ASM) cells were cultured at 37 ℃ and 5% CO₂ in dulbecco′s modified eagle medium (DMEM) cell medium. Cells at passages between 4 and 11 were divided into different groups according to the different compounds added. For control group, no compounds were administrated. For PDGF group, cells were stimulated with PDGF (20 μg/L) and cultured for an additional time. Cells were harvested and real-time PCR was used to measure mRNA level and Western blotting to detect protein level of HuR and TGF-β ₁ in ASM cells for different groups. Cells were divided into HuR siRNA group and control group. RNA-interference was used to determine whether lowering HuR expression could decrease PDGF-induced TGF-β₁ expression in HuR siRNA group and control group after the stimulation of PDGF for indicated times. Western blotting analysis was used to test the expression of TGF-β₁ after interrupting HuR expression. The concentration of TGF-β₁ in the cultured serum of HuR siRNA group and control group for 0, 6, 12 h under the stimulation of PDGF was measured by enzyme-link immunosorbent assay (ELISA). Cells were divided into control group, control+ PDGF 6 h group, HuR siRNA group and HuR siRNA+ PDGF 6 h group, then the half-life of TGF-β₁ mRNA in different groups was determined by treating ASM cells with the transcriptional inhibitor actinomycin D (10 mg/L) for 0, 4, 8 and 12 h.

PDGF treatment for 0, 6, 12 and 24 h significantly promoted HuR mRNA and protein expression and the relative levels were 1.00±0.00, 1.35±0.14, 1.73±0.17, 2.07±0.10; 0.51±0.10, 0.67±0.05, 0.83±0.07, 0.95±0.02 (all P<0.05). Similar alterations could also be demonstrated at TGF-β₁ mRNA and protein. The relative expression was 1.00±0.00, 1.27±0.06, 1.60±0.10, 1.87±0.10; 0.72±0.09, 0.87±0.07, 1.13±0.12, 1.33±0.05 (6 h versus 12 h and 12 h versus 24 h, P<0.05). HuR expression decreased 21.9% in HuR siRNA group compared with control group under the stimulation of PDGF for 12 h. HuR silencing also decreased PDGF-induced TGF-β₁ over-expression in ASM cells. In the control group, the relative protein levels of PDGF treatment for 0, 6 and 12 h were 0.70±0.05, 0.89±0.06, 1.06±0.05 and the protein levels in HuR siRNA group were 0.67±0.09, 0.77±0.03, 0.89±0.05 (all P<0.05). The concentration of TGF-β₁ in the cultured serum was measured by ELISA and the outcomes were (773.33±16.32, 877.97±16.03, 3 060.34±82.53) ng/L in control group for 0, 6 and 12 h. Under the same condition, the outcomes of HuR siRNA group were (277.33±9.93, 407.77±7.14, 828.05±11.67) ng/L (both P<0.05). Actinomycin D disturbed the process of transcription and the half-life of TGF-β₁ mRNA in HuR siRNA group showed no significant change compared with the HuR siRNA+ PDGF 6 h group (P>0.05). However, compared with control group and control + PDGF 6 h group, the half-life of TGF-β₁ mRNA in HuR siRNA group showed significant change (P<0.05).

PDGF can elevate TGF-β₁ expression in ASM cells. HuR regulates TGF-β₁ expression by promoting its mRNA stability.

To investigate the effect of steroid hormones on the growth and biofilm formation of S. epidermidis.

In all experiments, two S. epidermidis standard strains (ATCC12228 and ATCC35984) and two S. epidermidis clinical strains (SE101 and SE40) were incubated on the surface of silica gel in estradiol concentrations of 0, 50, 125, 250 and 500 pmol/L at 4, 6, 12, 24, 48 and 72 hours. Growth curve were drawn by means of the OD value. Formed biofilms were assessed by crystal violet staining methods. In order to observe the processes and structures of biofilm, the confocal laser scanning microscopy (CLSM) and scanning electron microscope (SEM) were used.

All of the four strains which were incubated with the concentrations of 125 pmol/L of estradiol had entered the logarithmic growth stage ahead of the blank control (3 h and 4 h). Crystal violet staining indicated that there was no biofilm for ATCC12228. Improved primary attachment abilities were found for ATCC35984 and SE101 in the presence of estradiol, and the OD values were 0 pmol/L (0.081±0.015 and 0.082±0.011), 50 pmol /L (0.087±0.013 and 0.088±0.010), 125 pmol/L (0.175±0.052 and 0.091±0.012), 250 pmol/L (0.153±0.036 and 0.090±0.006), 500 pmol/L (0.157±0.050 and 0.082±0.032), respectively. The thickness of biofilm reached the peak in 125 pmol/L estradiol at 24 h. CLSM and SEM found estradiol promoted the biofilm maturity and the biofilm of 125 pmol/L group was denser and thicker than that of the other concentration groups.

Our in vitro experiments indicate that estradiol could promote the growth of S. epidermidis which exit on the surface of silica gel, and improve the ability of biofilm formation of S. epidermidis.

To analyze the epidemic features of dyslipidemia among 39 980 Uygur, Kazak and Han ethnic groups in Urumqi, and to explore the methods of prevention and treatment on dyslipidemia.

The differences of blood total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) of health examination population with different ethnics, genders, and ages were compared, from 2012 to 2014 in the First Affiliated Hospital of Xinjiang Medical University.

Among the Uygur, Kazak and Han ethnic groups, the positive rate was respectively 35.0%, 37.0%, 30.3% in TC; 34.5%, 30.1% and 32.0% in TG; 24.9%, 18.3%, and 18.2% in HDL-C; 30.1%, 31.6% and 23.3% in LDL-C. In the same ethnic group, the abnormality rate of blood lipid in the female was lower than that of the male (P<0.001). The blood lipid abnormality rate increased significantly in those with 30-39 years, and reached the highest value in the 50-59 years group, then it decreased in those aged over 60 years (P<0.001).

The lipid abnormality rate of the Uygur and Kazak residents was higher than that of the Han nationality, and the abnormal levels of TC and LDL-C were particularly evident in Urumqi.

To determine the clinical effect of Friend-Ⅰ External Physical Vibration Lithecbole (EPVL) by Meta-analysis.

Pubmed, Embase, Medline, Cochrane Library, Chinese National Knowledge Infrastructure were searched for clinical trials comparing EPVL with the conventional treatment. The quality of included studies was assessed and Meta-analysis was conducted by Review Manager 5.3 software.

Five randomized or Quasi-randomized controlled trials met the inclusion criteria. The first day stone expulsion rate of EPVL group was superior to the control group (OR=4.95, 95% CI: 3.35-7.32, P<0.000 01). Both one-week (OR=3.13, 95% CI: 1.95-5.04, P<0.000 01) and two-week stone free rate (OR=4.50, 95% CI: 2.02-10.00, P=0.000 2) were statistically higher in the EPVL group than that in the control group. No severe adverse event occurred during the follow-up.

Our study suggested that EPVL could be the effective treatment for upper urinary tract residual stone. However, more high quality randomized controlled trials are needed to better affirm this.

Congenital adrenocortical hyperplasia (CAH) is a group of diseases caused by mutations in genes encoding enzymes essential for corticosteroid synthesis, resulting in disorders in the synthesis of adrenocortical steroids. Different degrees of enzyme deficiency also have different clinical manifestations. In recent years, with the continuous development of imaging technology, the detection rate of adrenal accidental tumor (AIs) has increased year by year^[1,2,3]。 There are reports in the world that AIs (often large tumor) was first diagnosed, and after clinical evaluation and longitudinal follow-up observation, the final diagnosis of non-classical CAH was confirmed^[4,5,6,7]； Studies on CYP21A2 gene mutation analysis in AIs patients also confirmed that 16% of AIs patients carried CAH mutation gene, and 2% were diagnosed with CAH^[8]。 We also encountered similar cases in our clinical work. After clinical evaluation and follow-up, it was finally confirmed that they were non-classical CAH. Whether it was an internationally reported case or a case confirmed by our hospital, there was misdiagnosis or missed diagnosis at the beginning, which suggests that clinicians should be more vigilant. Four patients admitted to the Department of Endocrinology of the General Hospital of the People's Liberation Army are reported as follows and related literatures are reviewed to improve clinicians' understanding of this disease.

A 53-year-old female was admitted to our hospital on June 5, 2014 due to "proposed acute myeloid leukemia (AML) for more than 2 months and after 2 cycles of chemotherapy". The patient went to the local hospital 2 months ago for persistent periumbilical pain. Blood routine showed: WBC 24.19×10⁹/L, hemoglobin 77 g/L, platelets 397×10⁹/L; Bone marrow image: hyperplasia was obviously active, with blast granulocytes accounting for 32.4%; Cytochemical staining: peroxidase (POX) staining was positive, chlorinated acetate AS-D naphtholesterase staining was partially positive, α-naphtholesterase acetate (α-NAE) staining was negative, alkaline phosphatase (NAP) positive rate was 82%, and the score was 264; Gene mutation: FLT3-ITD positive; Fusion gene screening was all negative; Chromosome normal karyotype; They were diagnosed as "AML-M2A with FLT3-ITD mutation, high risk group", and were given chemotherapy with DA regimen [daunorubicin 60 mg/d, days 1 to 3; cytarabine 100 mg every 12 hours, days 1 to 7) and CAT regimen (cyclophosphamide 300 mg every 12 hours, days 1 to 3; cytarabine 300 mg every 12 hours, days 2 to 6; topotecan 1.5 mg/d, days 2 to 6) on April 10, 2014 and May 4, 2014, respectively. After the end of chemotherapy, the bone marrow images reexamined showed no remission, and the proportion of blasts was 42% and 18%, respectively. Then he went to our hospital on June 5, 2014, and no obvious abnormalities were found in the admission physical examination. Blood routine: white blood cells 18.25×10⁹/L, hemoglobin 66 g/L, platelets 59×10⁹/L; There were no abnormalities in blood biochemistry; Bone marrow image: hyperplasia is obviously active, primitive and naive monocytes account for 78%, and mature monocytes account for 11.6%; Cytochemical staining: weakly positive for POX, positive for α-NAE, positive for sodium fluoride (NAF) inhibition test; Immunophenotype was detected by flow cytometry: the abnormal cell population accounted for 90.4% of nuclear cells, expressing CD117, CD13, CD33, CD36, and partially expressing CD38, conforming to the phenotype of AML; Gene mutation: FLT3-ITD positive; The modified diagnosis was "AML-M5 with FLT3-ITD mutation, high risk group" and sorafenib 400 mg was administered orally twice daily on 06 Jun 2014. On June 9, 2014, he was given chemotherapy with CLAG regimen [cladribine 7.5 mg/d continuous intravenous infusion, days 1 to 5; cytarabine 1.5 g every 12 hours, days 1 to 5; granulocyte colony stimulating factor (G-CSF) 300 μ g/d, days 0 to 5]. After chemotherapy, the bone marrow image was re-examined: hyperplasia was extremely reduced, and no blasts were seen. On July 9, 2014, the bone marrow image was re-examined: the hyperplasia was obviously active, and no blasts were seen; Blood routine on 20 Jul 2014: white blood cells 2.52×10⁹/L, hemoglobin 87 g/L, platelets 99×10⁹/L, neutrophils 1.51×10⁹/L, suggesting complete remission (CR). All-consistent allogeneic hematopoietic stem cell transplantation was followed.

Stress ulcer (SU) is a disease characterized by acute gastrointestinal erosion, ulcer and other lesions, which can eventually lead to gastrointestinal bleeding and perforation, and worsen the original lesions under various severe stress states such as severe trauma and critical diseases^[1]。 As early as 1999, the American Pharmacists Association (ASHP) issued the first guidelines for the prevention and treatment of stress ulcers, pointing out risk factors and preventive measures for SU, which are applicable to patients in intensive care units; In 2002, the editorial committee of Chinese medical journal formulated the interim standard for the prevention and treatment of stress ulcer^[2],The etiology, mechanism, clinical manifestations, diagnostic methods and preventive measures of SU were expounded. In recent years, domestic and foreign medical associations have revised the guidelines many times, and added the adapted objects and risk factors of drug prevention of SU. In 2009, the Department of General Surgery issued "Prevention and Treatment of Stress Mucosal Lesions in General Surgery-Suggestions of Chinese General Surgery Experts"^[3]The etiology, risk factors, diagnosis and preventive measures of stress mucosal lesions (SRMD) were given. In 2015, Bai Yu, Ren Xu, Li Zhaoshen and other expert groups on the prevention and treatment of stress ulcers updated the expert recommendations on the prevention and treatment of stress ulcers^[1]The Surgery Branch of the Chinese Medical Association also updated the expert consensus on the prevention and treatment of stress mucosal lesions^[4]It is again suggested that attention should be paid to the occurrence and development of SU in critically ill patients and the prevention of related complications. The above two guidelines are the current clinical prevention guidelines for SU in China, which give the prevention core of SU and SRMD and the treatment principles of complications in detail, and give the indications, strategies and measures of drug prevention. For the prevention of severe trauma and high-risk groups, proton pump inhibitors (PPIs) should be infused intravenously after the onset of the disease, so that the pH value in the stomach rapidly rises above 4.0, such as omeprazole (40 mg, twice/d). Prevention of SU is an important link in the prevention and treatment of gastrointestinal perforation and bleeding in critically ill patients. Rational use of PPIs to prevent stress ulcer is the key to successful treatment.

In 1922, Banting and Best successfully discovered insulin, declaring that diabetes was no longer an incurable disease, marking a new era of diabetes treatment. Since then, with the advent of various hypoglycemic drugs, the life span of diabetic patients has been significantly prolonged, but the harm of chronic complications of diabetes has gradually appeared, especially cardiovascular and cerebrovascular diseases, which have become the main cause of disability and death of diabetic patients. According to the British Diabetes Prospective Study (UKPDS), every 1% increase in glycosylated hemoglobin (HbA1c) can significantly increase the risk of myocardial infarction, heart failure, stroke, amputation, death and other events in patients with type 2 diabetes (T2DM)^[1]。 A large-scale observational study on complications and concomitant diseases of 239,000 patients with T2DM in 606 hospitals in China showed that common cardiovascular related diseases of T2DM include hypertension, dyslipidemia, coronary heart disease, cerebrovascular disease, etc. The prevalence rate of hypertension is as high as 33%, and the prevalence rate of coronary heart disease is 11%^[2]。 The ultimate goal of diabetes treatment is not only to achieve the standard of blood sugar control, but also to manage the risk of diabetic complications, especially the risk of cardiovascular diseases. Therefore, when evaluating hypoglycemic drugs, whether it can reduce or at least not increase the risk of cardiovascular events in patients is an issue that we must pay attention to.

Almost all nucleotide sequences in the human genome are transcribed, but less than 2% of the sequences are finally translated into proteins, and the vast majority of the remaining sequences are transcribed into non-coding RNA (ncRNA). According to their functions, ncRNAs can be divided into housekeeping ncRNAs, such as ribosomal RNA, transport RNA, and regulatory ncRNA, which can be divided into long non-coding RNA (lncRNA) and short chain ncRNA according to their length. Short-chain ncRNAs include well-known interfering RNAs (siRNAs), microRNAs (miRNAs), RNAs that interact with Piwi protein (piRNAs), and the like, and play an important role in mediating gene silencing at the transcriptional and post-transcriptional levels. lncRNA is a class of ncRNA with a length greater than 200 nucleotides. As early as the 1990s, it was found that lncRNA Xist was involved in the inactivation of X chromosome, and lncRNA H19 was involved in gene imprinting. With the implementation of the Human Genome Project and the widespread application of second-generation high-throughput sequencing technology, more and more lncRNAs have been discovered, and more than 28,000 lncRNA transcripts have been annotated at present (gencodegenes.org/stats/current.html). Most lncRNAs have similar structures to mRNA, but lack effective long open reading frames, have low conservation and high spatiotemporal specificity, and their expression is related to neighboring coding genes. According to their relationship with neighboring coding genes, they can be divided into cissense lncRNA, antisense lncRNA, bidirectional lncRNA, intron-derived lncRNA, and intergenic region-derived lncRNA (lincRNA). Through interaction with DNA, RNA and protein, they participate in various cellular processes such as gene imprinting, chromatin remodeling, mRNA splicing, synthesis and degradation, cell cycle regulation, etc., and regulate gene expression in many fields such as epigenetics, transcription and post-transcription, thus playing an important role in individual development and disease development^[1]。

Glucocorticoids are effective anti-inflammatory therapeutic agents for many inflammatory and immune diseases, especially inflammatory bowel disease, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, systemic lupus erythematosus, and others. However, some patients, even with large doses of glucocorticoids, still experience unresponsive or poor treatment effects^[1]This phenomenon is called glucocorticoid resistance. Due to the broad disease spectrum and increasing prevalence of chronic inflammatory diseases, the problem of glucocorticoid resistance also increases. It has been found that several mechanisms of glucocorticoid resistance have been described, including decreased expression of total glucocorticoid receptor (GR), increased expression of GR β, defects in GR binding ligand and nuclear transfer, activation of mitogen-activated protein (MAP) kinase pathway mediated by certain cytokines, overactivation of transcription factor activated protein 1, decreased expression of histone deacetvlase-2 (HDAC2), increased macrophage migration inhibitor, and increased drug excretion mediated by P-glycoprotein, etc^[1,2,3]。 It is well known that Th17 cells are involved in the pathophysiological processes of various inflammatory diseases and autoimmune diseases. Recent studies have found that glucocorticoid resistance is closely related to Th17 cells. Recent studies have shown that a specific phenotype of Th17 subtype-multidrug resistance gene 1 (MDR1)^＋Th17 cells play an important role in glucocorticoid resistance. In this paper, the recent advances in the study of glucocorticoid resistance mediated by Th17 cells are reviewed, with the aim of seeking strategies to reverse glucocorticoid resistance.

inflammatory bowel disease (IBD) is a class of chronic non-specific inflammatory diseases of the intestine, mainly including ulcerative colitis (UC) and Crohn's disease (CD). Epidemiological studies show that there are currently about 1 million CD patients and 1.4 million UC patients in Europe, while there are about 1.3 million IBD patients in the United States^[1]And the number of patients is still climbing. As an incurable disease, increasing IBD poses a serious challenge to patients' quality of life and global healthcare^[2]。 The incidence of IBD in China is increasing year by year, and related research started late, but developed rapidly in recent years. The pathogenesis of IBD has not been fully elucidated, and it is mainly caused by the interaction of environmental, genetic, infectious and immune factors^[3]。 At present, the main therapeutic drugs are aminosalicylic acids, glucocorticoids, immunosuppressants and biological agents, etc., all of which have different degrees of adverse reactions and treatment failure rates. It is urgent to explore effective therapeutic drugs to induce remission and maintenance therapy. Elafin is an endogenous serine protease inhibitor, which is a secreted protein and exists in mucosal epithelial cells and blood. Elafin can be used as an endogenous serine protease inhibitor to inhibit elastase, protease 3, pancreatic elastase and endogenous vascular elastase, and has the functions of anti-inflammation, immune regulation, anti-microbial infection, anti-cell proliferation, vascular remodeling, and participating in tissue damage repair^[4,5,6,7]。 In recent years, there are more and more studies on Elafin, and the research progress of Elafin in IBD will be reviewed.