Volume 99 ·  Issue 40 ·  2019

In this paper, some problems existing in the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) and the Guidelines for Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease formulated by China are questioned and suggested, including the definition of COPD, problems existing in diagnosis, prevention and control strategies, current goals and strategies of drug treatment, definition of acute exacerbation, assessment and management of comorbidities, and diagnosis and treatment of bronchial asthma and COPD overlap.

To investigate the characteristics of frailty in the elderly male patients with chronic kidney disease (CKD) and the effects of renal function on the incidence of frailty.

A total of 105 non-dialysis CKD patients aged ≥65 years who were admitted to the Chinese PLA General Hospital between October 1, 2018 and January 30, 2019 were included in this study. Their clinical data and laboratory indicators were collected. Frailty was defined according to Fried frailty criteria. According to the frailty scores, the participants were categorized as non-frail (n=37), intermediately frail (n=37) and frail (n=31). The association of frailty and the level of estimated glomerular filtration rate (eGFR) in the patients was analyzed using the model of multivariate Logistic regression.

Among the 105 patients, the mean age was 74 (68, 77) years old. The incidence of frail and intermediate frail was 35.2% (37/105) and 29.5% (31/105), respectively. Multivariate logistic analysis showed statistically significant associations of frailty with age (OR=1.14, 95%CI:1.08-1.20, P<0.001), body mass index (OR=0.87, 95%CI:0.79-0.95, P=0.001) and the level of eGFR (OR=0.98, 95%CI:0.96-0.99, P=0.003) in those patients. The incidence of frail in patients with eGFR<45 ml·min^-1·(1.73 m²)^-1 and 45-59 ml·min^-1·(1.73 m²)^-1 was 1.02 (OR=2.02, 95%CI: 1.06~3.87) and 0.84 (OR=1.84, 95%CI: 1.05-3.22) times higher than that of eGFR≥60 ml·min^-1·(1.73 m²)^-1, respectively.

The incidence of frailty in the elderly patients with CKD is affected by many factors, such as age, body mass index and renal function, and increases with decreased renal function.

To investigate the correlation between serum bilirubin and cardiovascular autonomic neuropathy (CAN) in type 2 diabetes mellitus patients.

A total of 369 patients with type 2 diabetes mellitus who were hospitalized at the Department of Endocrinology, Nanjing Jinling Hospital from April 2017 to October 2018 were enrolled, including 226 males and 143 females, with an average age of (54.6±12.1) years. According to cardiovascular reflex tests (CARTs), all the patients were divided into Non CAN group(149 patients without CAN) and CAN group (220 patients complicated with CAN). The difference of serum bilirubin levels between the two groups was compared. The differences of CARTs and the incidence of CAN were compared by tertiles of serum bilirubin levels. The binary logistic regression was used to analyze the risk factors for diabetic cardiovascular autonomic neuropathy.

The serum total bilirubin [(9.28±2.74) μmol/L vs (11.08±2.98) μmol/L, P<0.001], direct bilirubin [(3.17±1.20) μmol/L vs (3.71±1.24) μmol/L, P<0.001] and indirect bilirubin levels [(6.11±1.89) μmol/L vs (7.37±2.10) μmol/L, P<0.001] in CAN group were significantly lower than that in Non CAN group. With the increase of serum bilirubin, the incidence of CAN decreased (P<0.01). Multivariate Logistic regression analysis showed that serum total bilirubin (OR=0.819, 95%CI: 0.744-0.901, P<0.001), direct bilirubin (OR=0.739, 95%CI: 0.601-0.908, P=0.004) and indirect bilirubin (OR=0.749, 95%CI: 0.653-0.860, P<0.001) were inversely correlated with the incidence of CAN.

Within the physiological range, lower level of serum bilirubin is inversely correlated with the incidence of CAN. It is noteworthy to screen diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus who had a lower serum bilirubin level.

To investigate the efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio (LMR) in patients with diffuse large B-cell lymphoma (DLBCL).

The clinical data of 261 patients with DLBCL in the Affiliated Cancer Hospital of Zhengzhou University between March 2012 to March 2018, were analyzed retrospectively. The optimal cut-off values of LMR was determined using the receiver operating characteristic curve (ROC) method. Patients were divided into low LMR group and high LMR group according to the optimal cut-off value. The changes of LMR before and after treatment in two groups were dynamically monitored, and the relationship between LMR and efficacy and survival were analyzed.

Complete remission (CR) rate in patients with high LMR (64.7%) before treatment was significantly higher than that in patients with low LMR (33.3%) (P<0.05). Compared with the 5-year overall survival(OS) and progress free survival(PFS) (56.96% and 43.55%, respectively) in the low LMR group, the 5-year OS and PFS (82.92% and 66.25%, respectively) in the high LMR group were higher, and the difference was statistically significant (all P<0.05). Patients with elevated LMR after treatment in the high or low LMR group had a significant higher 5-year OS and PFS compared with patients with LMR reduction(P<0.05). LMR in both high and low LMR group were significantly lower at the last follow-up than those at the disease recurrence (all P<0.05). Both single and multivariate analyses showed that low LMR was an independent prognostic factor in patients with DLBCL (all P<0.05).

LMR can be used as an indicator of risk stratification, efficacy, disease replase and prognosis in patients with DLBCL. Low LMR before and after treatment were poor prognostic factors in patients with DLBCL.

To analyze the distribution of gene mutations in newly diagnosed acute myeloid leukemia (AML) patients, based on next generation sequencing technology (NGS) and to evaluate their value in AML risk stratification.

The study analyzed 453 newly diagnosed AML(excluded acute promyelocytic leukemia, APL) patients from seven hospitals in Shanghai, from January 1st 2014 to December 31th 2017. RNA and DNA were extracted from pretreatment bone marrow mononuclear cells and targeted sequencing of AML genes were performed. The data of different groups was compared.

A total of 453 newly diagnosed AML patients were enrolled in the study, including 247 males and 206 females with a median age of 49.5 (range,11-85) years. A total of 540 mutations/fusion genes were detected in 289 patients, 29.1% (132/259) of whom with two or more mutations/fusion genes. In all patients, NPM1 was the most common mutation(12.8%), followed by ETO and TET2 mutation (11.92% and 11.04%, respectively) . And WT1 over-expression accounted for 10.6%. Patients over the age of 50 were with a higher frequency of mutations associated with epigenetic modification, 11.93% for ASXL1, 13.99% for DMNT3A, 6.58% for IDH1/IDH2, and 13.17% for TET2. The frequency of DMNT3A mutations was three times higher than that of patients under 50 years of age (P=0.017). In this study, a relatively low proportion of genetic mutations was observed in low-risk karyotype group. In the medium-risk karyotype group, the relatively high mutation frequencies were observed in NPM1, TET2, FLT3-ITD, DNMT3A, ASXL1, and CEBPA genes. In the poor-risk karyotype group, the mutation frequencies of ASXL1, TET2, DNMT3A and PHF6 genes were more than 10%, especially ASXL1 and PHF6 mutation frequencies were significantly higher than other molecular risk stratification groups (P<0.05). Of the 254 patients (56%) with normal karyotype AML (NK-AML), 56 patients were detected to have gene mutations about epigenetic modification. The median OS of this group was worse than that of patients without related mutations, while the median LFS had no significant difference. In patients with NK-AML older than 50 years, the OS and LFS of patients with epigenetic modification related gene mutations was 12 months and 10 months, versus 18 months and 12 months of patients without mutations.

The gene mutations frequencies in AML patients with different age and molecular risk stratification groups are different. Epigenetics gene mutation frequencies, such as DNMT3A, ASXL1, IDH1/IDH2 and TET2,are higher in patients older than 50 years. A shorter OS can be observed in older patients(>50 years) with epigenetics gene mutation.

To explore the coexisting mutations in NPM1 mutated elderly patients with acute myeloid leukemia(AML).

The clinical data of 152 elderly adults(aged≥60 years) and 49 young adults(aged 18-45 years) with AML between June 2013 and December 2018 in outpatient and hospitalized patients of Changzhou Second People′s Hospital and Wuxi Second People′s Hospital were retrospectively analyzed. A total of 51 gene mutations were detected using targeted next-generation sequencing (NGS) and sanger sequencing. The general clinical characteristics, the occurrence of coexistence gene mutations, the correlation between coexistence gene mutations and some clinical parameters, and the initial induction remission rate between elderly and young adult AML patients with NPM1 mutations were analyzed and compared.

NPM1 mutations were detected in 46 of 152 elderly AML patients. Thirty eight patients (82.6%) with NPM1 mutations carried other gene mutations at the same time, among whom 8 patients (17.4%) carried NPM1 mutations alone, while 14(30.4%) carried 2, 16 (34.8%) carried 3, and 8 (17.4%) carried ≥ 4 mutations. NPM1 mutations frequently co-occurred with FLT3-ITD15 cases (32.6%) , DNMT3A10 (21.7%) , TET26 (13.4%) and FLT3-TKD5 (10.9%) . Compared with young adults with NPM1 mutations, elderly patients had higher TP53, FLT3-TKD rates, lower incidence of DNMT3A, RAS mutation (all P<0.05) and lower coexistence rate of 4 gene mutations (P=0.002).The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than those in patients with single, double and 3 mutations coexisted in elderly adults AML patients(all P<0.05). With the increase of the amount of mutations, the complete remission(CR) rate decreased gradually after the initial induction. Patients who carried 3 or more mutations showed a lower CR rate than those with single gene mutations (all P<0.05) . Patients who carried>4 genes also showed a significantly lower CR rate than those with double gene mutations (P=0.031). Patients with FLT3-ITD mutations exhibited higher white blood level and lower CR rate than that in nonmutant type group (all P<0.05). The CR rate of patients with DNMT3A mutation was also significantly lower than that with nonmutant type (P=0.033). However, patients with FLT3-TKD mutations showed a higher platelet level than that with nonmutant type (P=0.019). There was no significant difference in CR rate and peripheral blood cell level between TET2 mutated and nonmutant type.

NPM1 mutated elderly patients with AML commonly show additional mutations, and the amount and type of coexisting mutations have an influence on the clinical features and CR rate of elderly patients with AML.

To assess the oncologic outcomes of radical nephroureterectomy (RNU) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC).

From January 2014, all high-risk UTUC patients after RNU surgery were enrolled in this prospective comparative trial. And these patients were randomized to ACT group (Gemcitabine+Cisplatin three weeks regimen) and observing group. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall survival (OS), cancer specific survival (CSS) and disease-free survival (PFS) in the cohort.

The median follow-up duration was36 months (range: 6-54) in the ACT group (n=94) and 30 months (range: 6-54) in the observing group (n=82). Oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT: OS [P=0.0397, HR: 1.39(0.91-1.75)], CSS [P=0.0255, HR: 1.26(1.07-1.45)] and PFS [P=0.0033, HR: 3.78(3.13-4.55)]. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the ACT group compared with the observing group: OS (26.8mon vs 36.3mon, P=0.0255), CSS (28.2mon vs39.3mon, P=0.0197) and PFS (11.4mon vs 31.9mon, P=0.0018). Additionally in T3/4 cohort, the significant growth in the median times of OS (20.6mon vs 32.2mon, P=0.0183), CSS (21.9mon vs 38.4mon, P=0.0226) and PFS (13.9mon vs 36.3mon, P=0.0217) were observed in ACT group.

ACT could play the important synergistic role in improving the OS, CSS and PFS of high-risk UTUC patients after RNU.

To investigate the effect of optimized preoperative dietary management on enhanced recovery in patient with consecutive operation of robot-assisted radical prostatectomy(RARP) at night.

Forty patients undergoing consecutive operation of robot-assisted radical prostatectomy at night in the department of urology in our hospital from Jun 2018 to March 2019 were divided into two groups, 23 patients in the study group and 17 patients in the control group. The control group followed the traditional fasting program at 24∶00 p.m. the day before the surgery. In the study group, the preoperative fasting procedure was optimized. The fasting time, water deprivation time, intravenous infusion volume, scores of hunger and thirst, blood glucose level, length of postoperative hospital stay and adverse reactions were compared between two groups. The level of hunger and thirst were evaluated using the Likert score.

The preoperative fasting time and water deprivation time of the study group and the control group were (11.9±4.4 vs 19.3±4.8) h and (6.0±2.9 vs 19.3±4.8) h, respectively (P<0.01). The infusion volume of study group was (406.5±310.5) ml and that of control group (744.1±443.0) ml, the difference was statistically significant (P<0.01). The hunger and thirst scores of the study group were lower than those of the control group before surgery, and the postoperative hospital stay was shorter than the control group (P<0.05).

The optimized preoperative dietary management shortens fasting and water deprivation time, reduces the intravenous infusion volume, relieves the hungry and thirsty in patients with consecutive operation of robot-assisted radical prostatectomy at night.

To investigate the clinical characteristics and risk factors of cytomegalovirus (CMV) reactivation in immunocompetent patients in respiratory intensive care unit (RICU).

Clinical data of immunocompetent patients whose serum CMV-DNA was monitored during hospitalization in the RICU of Peking University First Hospital from July 2014 to July 2018 were collected and reviewed in this retrospective study. Patients were divided into the CMV reactivation group and non reactivation group. Demographics, clinical features, and outcomes of patients in the two groups were analyzed. The multivariable logistic regression analysis was used to analyze the independent risk factors for CMV reactivation.

Of the 81 patients, 11 (13.6%) were in the reactivation group and 70 (86.4%) were in the non reactivation group. Length of RICU stay were longer in the group with CMV reactivation compared to patients without CMV reactivation [54(50, 68) vs 32(17, 43) d, P=0.012]. Baseline demographic and disease characteristics, rate of ventilator-associated pneumonia, duration of mechanical ventilation and mortality were similar in the two groups. Multivariable logistic regression analysis showed that blood transfusion (OR=11.481, 95%CI: 1.154-114.201; P=0.037) and corticosteroids use (OR=13.952, 95%CI: 2.301-84.609; P=0.004) were independent risk factors for CMV reactivation.

CMV reactivation is associated with a longer stay in the RICU in immunocompetent patients, blood transfusion and corticosteroids use constitute risk factors.

To evaluate the diagnostic value of the serum Krebs von den Lungen-6 (KL-6) for the interstitial lung disease associated with connective tissue diseases (CTD-ILD).

84 patients with CTD-ILD (CTD-ILD group) and 91 patients with connective tissue disease (CTD group) who visited the department of rheumatology and immunology of People′s Hospital of Xinjiang Uygur Autonomous Region between January, 2016 and December, 2017 were included. Serum KL-6 levels were measured by commercially available enzyme linked immunosorbent assay (ELISA) kits.

The significantly higher levels of KL-6 were determined in the CTD-ILD group than CTD group [1 239 (577, 2 094) vs 152 (89, 280) U/ml] (P<0.001). The optimal cutoff value of serum KL-6 for diagnosis of CTD-ILD was 402 U/ml, and the sensitivity and specificity were 82.1% and 86.8%, respectively. Area Under the Curve (AUC) was 0.905. Logistic regression analysis revealed that elevated KL-6 and decreased Carbon monoxide diffusion capacity were independently correlated with the occurrence of CTD-ILD, the decreased of DLcoSB% (OR=0.928, 95%CI: 0.891-0.968) and increase of KL-6 level (OR=1.005, 95%CI: 1.003-1.007) was the independent risk factor for the occurrence of ILD.

The serum KL-6 is an important biomarker for the diagnosis of CTD-ILD and when the level of KL-6 is increased, the ILD should be alert.

To investigate the protective effect of Baicalin on apoptosis induced by lipopolysaccharide in H9C2 cardiomyocytes and its possible mechanism.

In order to establish apoptosis model of H9C2 cardiomyocytes, H9C2 cardiomyocytes were cultured and divided into four groups: the control group; the baicalin group was treated with baicalin at the final concentration of 10μmol/L for 12 hours; the LPS group was stimulated with LPS at the final concentration of 1 μg/ml for 6 hours; The LPS+baicalin group was stimulated with LPS at the final concentration of 1 μg/ml for 6 hours within treated with baicalin at the final concentration of 10μmol/L for 12 hours. Collecting cell samples, CCK-8 (The Cell Counting Kit-8) was used to detect cell activity, and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) was used to detect the expression levels of apoptosis. Laser Scanning Confocal Microscopy was used to detect the expression levels of store-operated calcium entry in H9C2 cardiomyocytes. Western blot was used to detect the protein expression levels of STIM1, cleaved-caspase3, Bax and Bcl-2. Fluorogenic quantitative PCR was used to detect the mRNA expression level of STIM1.

Compared with the control group, LPS-induced H9C2 cardiomyocyte survival rate decreased (P<0.05), the expression level of apoptosis increased (P<0.05), the internal flow of calcium increased (P<0.05), the expression levels of cleaved-caspase3, Bax protein levels increased (P<0.05), Bcl-2 protein level decreased (P<0.05), the expression of STIM1 mRNA and protein level increased (P<0.05). Compared with LPS group, the survival rate of H9C2 cardiomyocytes in baicalin intervention group increased (P<0.05), the expression level of apoptosis decreased (P<0.05), the internal flow of calcium decreased (P<0.05), the expression levels of cleaved-caspase3, Bax protein decreased (P<0.05), and the level of Bcl-2 protein increased (P<0.05), the expression of STIM1 mRNA and protein level decreased (P<0.05).

Baicalin may alleviate LPS-induced cardiomyocyte apoptosis by alleviating calcium overload, and improve cell survival.

Good syndrome is an adult immunodeficiency disease characterized by thymoma and hypogammaglobulinemia. Its humoral immunity and cellular immunity are deficient, and its clinical manifestations are often repeated infections. However, Good syndrome complicated by Pneumocystis jiroveci pneumonia (PJP) is rarely reported in the literature. This case was reported as a patient with type B2 thymoma. Pneumocystis jiroelii was detected in sputum and alveolar lavage fluid, which was confirmed to be PJP. At the same time, blood IgG and IgM decreased, absolute value of T lymphocytes, absolute value of B lymphocytes, absolute value of CD4 T cells and CD4⁺/CD8⁺The ratios all decreased significantly, which was in line with the diagnosis of Good syndrome.

This article reports a case of a middle-aged male patient with anorexia, repeated fever, jaundice, and significantly increased blood pancreatic enzymes. After being transferred to many hospitals for anti-infective treatment, it was ineffective. The initial diagnosis impression was that biliary acute pancreatitis was considered, and the possibility caused by other diseases was ignored. After detailed medical history and further examination, brucellosis was finally diagnosed. In recent years, the incidence of brucellosis in China has been increasing, but due to the atypical clinical manifestations and the lack of detailed contact history inquiry of epidemic sources, it is easy to be ignored by clinicians and delay the diagnosis. Brucellosis with pancreatic involvement is very rare, and patients are seriously ill and prone to serious consequences due to misdiagnosis.

This article describes the diagnosis and treatment of a young male patient with chronic diarrhea and recurrent hematochezia. Extragastrointestinal manifestations such as skin thickening and joint symptoms are the breakthrough points in diagnosis. On the basis of multidisciplinary cooperation, it took nearly 4 years to explain the whole picture of the disease with monism from the diagnosis of primary hypertrophic osteoarthropathy (PHO) and the discovery of SCLO2A1 gene mutation to the final definitive diagnosis. At present, there is still a lack of systematic understanding of SCLO2A1 gene-related chronic bowel disease, and its characteristics are different from common known diseases that can cause intestinal ulcers. In the absence of a clear and effective treatment plan, the most basic enteral nutrition therapy can instead obtain better results.

A case of IgA-predominant glomerulonephritis after acute streptococcal infection is reported. This disease is a rare and special type of infectious glomerulonephritis, which is more common in elderly patients with diabetes and low immunity, and has nephritic syndrome-like manifestations. However, this case was a young female patient without the above-mentioned underlying diseases and mainly with nephrotic syndrome, and her condition was relieved after simple conservative treatment (without immunomodulatory therapy). After 10 months follow-up, urine protein turned negative and serum creatinine was normal.

To date, there have been few studies on olfactory dysfunction after pituitary adenoma resection through the nasosphenoidal approach, and the results are inconsistent. This article reviews the related studies on the effects of transnasal sphenoidal pituitary adenoma surgery on olfactory function and compares the different surgical details. The results showed that direct injury of olfactory mucosa and obstruction of nasal airflow were the main causes of postoperative olfactory disturbance; Compared with microscopy, endoscopic transsphenoidal pituitary adenoma resection has certain advantages in preserving olfactory function; Intraoperative preparation of nasal mucosal flap may aggravate postoperative olfactory loss. However, at present, the level of evidence-based evidence in relevant studies is low, and the quality control of research is insufficient. It is urgent to carry out prospective randomized controlled studies to clarify the true incidence of olfactory dysfunction after transsphenoid pituitary adenoma surgery, and at the same time, further improve and optimize the surgical methods to facilitate the preservation of olfactory sense.

Centromeric protein B (CENP-B) is a DNA-binding protein that can specifically bind to highly repeated 17 bp nucleotide sequences in α-satellite DNA. It participates in the formation of centromeric-kinetomeric complex (CKC), which is closely related to cell proliferation and chromosome segregation. Abnormality or deficiency of CENP-B will lead to changes in CKC morphology and function, increase chromosome instability, lead to gene mutation, and thus promote tumor development. This paper focuses on the structure, properties, functions of CENP-B and the relationship with tumor, which provides theoretical basis for exploring the mystery of cell cycle and provides new research targets for the treatment of tumor and other related diseases.