Volume 99 ·  Issue 20 ·  2019

Currently H. pylori (H. pylori) Treatment of infections faces severe challenges, and how to improveH. pyloriThe eradication rate is a hot topic in current research. This article introduces the relevant concepts and principles of the "National Consensus on Integrated Treatment of Helicobacter Pylori-Related Diseases with Integrated Traditional Chinese and Western Medicine" published in 2018, aiming to clarify how to correctly understand and apply the consensus, and how to define "refractoryH. pyloriInfection "and its management principles and strategies, what is"H. pyloriCurrent clinicians are extremely concerned about, andH. pyloriIssues focused on by the research.

In recent years, the long-term prognosis of liver transplant recipients has improved significantly, mainly thanks to the use of immunosuppressive agents. A major problem affecting prognosis is the emergence of new tumors over time. In this paper, the relationship between the development of new tumors and chronic immunosuppressive status, physiological aging, chronic viral infection, lifestyle, etiology of liver disease and carcinogenic effect of certain immunosuppressants are described in detail in combination with relevant literatures. Moreover, the monitoring of new tumors after surgery, screening more effective treatment measures for different tumors, and putting forward evidence for reference.

Surgery is the most important treatment for PMP. In the past, biopsy, (repeated) tumor reduction, combined with systemic chemotherapy and (or) intraperitoneal chemotherapy were mainly adopted. Although the surgical procedure was simple and less invasive, patients were prone to recurrence after operation, and the clinical efficacy was poor^[14,15,16]。 1980 Spratt et al.^[17]Tumor cytoreductive surgery (CRS) plus intraperitoneal hyperthermia infusion chemotherapy (HIPEC) was introduced for the first time, which provided a new idea for PMP treatment. 2001 Sugarbaker^[18]CRS + HIPEC + early postoperative intraperitoneal chemotherapy (EIPC) was systematically studied, proving that this therapy is the best strategy for PMP. In 2008, PSOGI reached an expert consensus on CRS + HIPEC treatment for PMP^[16]。 2012 Chua et al.^[19]A detailed analysis of 2,298 PMP treatment data in multicenters worldwide showed that standardized CRS + HIPEC can prolong overall Survival (OS) by 196 months (16.3 years) and Progression Free Survival (PFS) by 98 months (8.2 years), with a 10-year Survival rate of 63% and a 15-year Survival rate of 59%. Due to these outstanding efficacies, in 2014, PSOGI held the 9th International Peritoneal Cancer Congress in the Netherlands and officially recommended CRS + HIPEC as the standard treatment for PMP^[20]。

To evaluate the efficacy and safety of tetracycline and metronidazole based quadruple regimen as first line treatment for penicillin allergic patients with Helicobacter pylori (H.pylori) infection.

The clinical data of 120 patients who had infected with H. pylori and were allergic to penicillin in out-patient clinic of Peking University First Hospital was retrospectively collected from January 2014 to June 2016. The regimen included: lansoprazole 30 mg twice a day+ Bismuth 150 mg three times a day+ tetracycline 500 mg three times a day+ metronidazole 400 mg three times a day, for 14 days. All patients were followed up 7 days, 14 days, at least 4 weeks after the treatment. Symptoms and side effects were recorded. The H.pylori status was evaluated by ¹³C urease breath test at least 4 weeks after the end of the treatment.

All patients included 86 female and 34 male, and the average age is 59 years. There are 104 of the 120 cases who got success in eradication treatment. Mild to moderate adverse effects occurred in 56 cases (46.7%). 10 female patients dropped out because of headache, rash, vomiting and fatigue. The eradication rates were 86.7% (104/120, ITT) and 94.5% (104/110, PP).

Tetracycline and metronidazole based 14-day quadruple regimen is effective as first line treatment for penicillin allergic patients with H. pylori infection because of its relatively high eradication rate. Patients should be watched closely during the treatment since the adverse effects of this regimen happen frequently,especially for female patients.

To investigate the therapeutic effect of compound allantoin in Kunming mice infected with Helicobacter pylori (H. pylori).

Eighty four male Kunming mice were randomly divided into normal control group, H. pylori infection control group, compound allantoin group, allantoin group, aluminum hydroxide group, triple therapy group, and compound allantoin combined with triple therapy group(drug combination group). The normal control group was administered with normal saline, and other groups were infected with H. pylori for 5 times by intragastric(IG) administration. After 4 weeks, mice were given corresponding drug solutions for 6 times by IG administration. H. pylori infection status was detected by rapid urease test(RUT) and immunohistochemistry assay(IHC). Mucosa damages were assessed by microscopic examination and electron microscopy.

The positive rates of the compound allantoin group detected by RUT and IHC were 9.1% and 0, respectively, which were significantly lower than those in the H. pylori infection control group (81.8% and 72.7%).The positive rates of aluminum hydroxide group(54.5% and 54.5%) have no significant difference with those in the allantoin group (27.3% and 18.2%), but were higher than those of compound allantoin group (P<0.05).The positive rate of both methods in the drug combination group were 0, and they were significantly lower than those in the triple therapy group (36.4%,45.5%) (P<0.05). There was no difference between the triple group and the compound allantoin group(P>0.05). The pathological and ultrastructural damage of compound allantoin group was obviously relieved than that of H. pylori infection group.

Compound allantoin has therapeutic effect on H. pylori infection in mice, which can be further enhanced by combination with triple therapy group. In addition, compound allantoin can repair gastric mucosal injury caused by H. pylori, and its repair effect may be related to mitochondrial pathway.

To investigate the effects of sucralfate suspension gel (SC) on Helicobacter pylori (H.pylori) colonization, H.pylori-induced gastric mucosal injury and gastrointestinal microecology in mice.

C57BL/6J mice were randomly divided into 3 groups, including normal control (NC) group, H.pylori model (HP) group, and SC prevention (HP+SC) group. H.pylori infection mouse model was established by gavage with H.pylori Sydney strain (SS1). And HP+SC group was also administered with SC for 14 days. After mice were sacrificed, the gastric mucosa was taken for HE staining, immunohistochemical (IHC) staining [H.pylori, zonula occludens-1 (ZO-1), Occludin, interleukin (IL)-8, IL-10 and tumor necrosis factor-α (TNF-α)], qPCR (IL-8, IL-10, TNF-α) . And cell ultrastructure was observed by electron microscopy. Microbiota communities in the gastric mucosa or fecal were investigated using 16S ribosomal RNA (rRNA) gene sequencing. The detection ofH.pylori in IHC staining or Giemsa staining was defined as H.pylori infection.

The H.pylori positive rate of HP group was 91.67%, and that of HP+SC group was 50.00%. The EDS of HP group were significantly higher than those of the NC group [(3.42±0.19) vs (1.17±0.17), P<0.05], while EDS of HP+SC group (2.42±0.29) were significantly lower than that of HP group (P<0.05). The mRNA levels and immunostaining scores of IL-8, IL-10 and TNF-α in HP group was higher than NC group (allP<0.05). Compared with HP group, mRNA levels and IHC scores of IL-8 significantly decreased (all P<0.05) in HP+SC group, while those of IL-10 and TNF-α was similar between two groups (allP>0.05). The IHC scores of ZO-1 and Occludin in HP group was significantly lower than NC group (all P<0.05), and that of ZO-1 and Occludin in the HP+SC group increased compared with HP group [(2.00±0.26) vs (1.17±0.48), P>0.05; (3.50±0.43) vs (2.33±0.21), P<0.05]. Compared with NC group, the diversity of gastric microbiota in HP group was significantly lower, and diversity of gut microbiota decreased insignificantly. There was no significant difference between HP+SC group and HP group in gastric or gut microbiota.

SC reduces H.pylori colonization, protects H.pylori-induced gastric mucosal injury, decreases H.pylori-induced IL-8 expression, enhances Occludin. However, its effects on H.pylori-induced gastrointestinal microbiota disorders are limited.

To investigate the expression and prognosis effect of methylation-regulated SLIT3 and SPRCL1 genes in smoking-related lung adenocarcinoma.

The expression levels of SLIT3 and SPARCL1 in cigarette smoke-induced malignant transformed cell (S30) and lung adenocarcinoma (LUAD) cell lines were measured by real-time fluorescence quantitative PCR (qPCR). Datasets of mRNA expression, DNA methylation and patient information data were obtained from The Cancer Genome Altas (TCGA) database. The mRNA expression levels of SLIT3 and SPARCL1 were validated in LUAD tissues. The 10-year survival curve of LUAD patients with different smoking history was plotted, and the correlation between mRNA expression level and DNA methylation level of LUAD patients was further analyzed. S30 cells were treated with 5-azacytidine (5-aza), an inhibitor of DNA methyltransferase, to analyze the methylation regulatory mechanism of SLIT3 and SPRCL1.

The qPCR results showed the significant down-regulation of SLIT3 and SPARCL1 in S30 cell and four LUAD cell lines (SLIT3: 0.493±0.134 and 0.041±0.014, 0.161±0.023, 0.277±0.055, 0.035±0.005; SPARCL1: 0.507±0.131 and 0.453±0.045, 0.420±0.040, 0.153±0.035, 0.430±0.050; all P<0.01). Bioinformatics analysis showed that SLIT3 and SPARCL1 were low expressed in LUAD tissue (8.12±1.58 vs 10.84±0.69 and 11.46±1.06 vs 13.57±0.67; both P<0.001) compared with adjacent peritumoral tissues, and expression levels of SLIT3 and SPARCL1 were significantly correlated with smoking history (both P<0.001). Non-smoker with high expression of SLIT3 and SPARCL1 was associated with better prognosis among LUAD patients. There was a significant negative correlation between promoter methylation and mRNA expression level of the two genes (r=-0.208, -0.574; both P<0.001). 5-aza treatment significantly up-regulated the expression levels of SLIT3 and SPARCL1 genes in S30 cells (2.137±0.281, 3.657±0.882; both P<0.01).

SLIT3 and SPARCL1 can be regulated by DNA methylation and down-regulated in LUAD tissue, which has important prognostic significance on the smoking-induced LUAD patients.

To explore the clinical characteristics and microsurgical strategies of intracranial posterior circulation aneurysms.

The clinical manifestations, imaging data, surgical approaches and follow-up results of 35 patients with circulating aneurysms (37 aneurysms) treated by microsurgery in the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2018 were analyzed retrospectively.

A total of 22 aneurysms were clipped, 13 were clipped and resected, 1 case was clipped and together with AVM resection and 1 case was isolated. Of 37 aneurysms in 35 patients, 11 aneurysms were at the basilar artery apexes, 10 at the posterior cerebral arteries, 6 at the posterior inferior cerebellar arteries, 3 at the basilar arteries, 3 at the vertebral arteries (including 1 case of vertebral arterial dissecting aneurysm), 2 at the anterior inferior cerebellar arteries and 2 at the superior cerebellar arteries. The surgical approaches included pterional approach, extensive pterional approach, infratemporal fossa approach, retrosigmoid approach and far-lateral approach. The Glasgow Outcome Scale (GOS) scores showed good recovery in 24 cases, moderate neurological dysfunction in 6 cases, severe neurological dysfunction in 2 cases, persistent vegetative state in 1 case and 2 cases of death 6 months after their discharge from hospital.

Posterior circulation aneurysms are adjacent to important structures. They are deep in position, with small operation space and difficult to operate. Full preoperative evaluation of the condition, selection of appropriate surgical methods are the key factors to benefit the patients.

To investigate the effect of Toll-like receptor 7 (TLR7) in CD8⁺ T cells activity from patients with breast cancer.

Thirty-three patients with breast cancer, twenty-three patients with benign breast tumor, and twenty healthy individuals were collected from The First Affiliated Hospital of Xinxiang Medical University between December 2017 and March 2018. Peripheral blood mononuclear cells (PBMCs) were isolated, and CD8⁺ T cells were purified. TLR7 protein and mRNA relative expression in CD8⁺ T cells was measured using flow cytometry and real-time PCR, respectively. mRNA relative expressions corresponding to perforin, granzyme B, and FasL in CD8⁺ T cells were measured in response to TLR7 agonist stimulation. Direct/indirect contact co-culture system of CD8⁺ T cells and breast cancer cell line MCF-7 was also used to assess cytolytic and noncytolytic function in response to TLR7 agonist CL097 stimulation.

The mean fluorescence intensity corresponding to TLR7 protein in CD8⁺ T cells from breast cancer patients was 124.0±15.32, which was significantly down-regulated in comparison with benign breast tumor patients (255.5±54.91) and healthy individuals (261.9±68.65) (P<0.000 1). TLR7 mRNA relative level was also remarkably reduced in CD8⁺ T cells from breast cancer patients (1.97±1.18) in comparison with benign breast tumor patients (4.84±1.01) and healthy individuals (4.75±1.40) (P<0.000 1). TLR7 agonist CL097 stimulation notably increased mRNA relative levels of perforin and granzyme B mRNA in CD8⁺ T cells (P<0.01), but not elevated FasL mRNA (P>0.05).Furthermore, TLR7 agonist CL097 stimulation enhanced the cytolytic and noncytolytic function of CD8⁺ T cells to MCF-7 cells, which presented as the elevation of target cell death and increase of interferon-γ production in direct and indirect contact co-culture system.

TLR7 agonist promoted CD8⁺ T cells function from breast cancer patients.

To analyze the influencing factors of protein energy wasting (PEW) in maintenance hemodialysis (MHD) patients.

A multicenter cross-sectional study was conducted in eleven hemodialysis centers of Guizhou province between June and August 2018. Clinical data, physical parameters, body composition data and laboratory values of MHD patients were collected. Analysis of variance was used to assess the impact of the indicators on the prevalence of PEW. Factor analysis was carried out after further classifing the factors into several common factors, and logistic regression was used to analyze the impact of common factors on PEW.

The results of univariate analysis showed that somatic cell mass, lean weight, fat content, body mass index (BMI), grip strength, leg circumference, hip circumference, waist circumference, midpoint circumference of upper arm, triceps skin fold thickness, hemoglobin, albumin, prealbumin, serum calcium, phosphorus, serum magnesium, creatinine, parathyroid hormone were the influential factors of PEW (all P<0.05). Factor analysis indicated that the above indicators can be classified into five common factors. Logistic regression model showed that with the increase of the prevalence of PEW, the scores of common factors decreased, the absolute value of regression coefficient beta in sequence, was common factor 2 (β=-2.258,P<0.001), common factor 4 (β=-1.589,P<0.001), common factor 1 (β=-1.144,P=0.001) and common factor 3 (β=-0.740,P=0.016).

The reduction of fat content, anemia, hypoproteinemia, disorder of calcium and phosphorus metabolism were important factors influencing PEW.

To determine the incidence of unplanned reoperation following vitreoretinal surgery and identify the reasons for unplanned reoperations.

Case records of all patients undergoing vitreoretinal surgery at Peking Union Medical College Hospital between June 2014 and June 2017 were reviewed to determine the incidence of unplanned reoperations during the primary admission and within 90 days following vitreoretinal surgery.

A total of 3 356 case records were reviewed. During the primary admission, 97 times of unplanned reoperation occurred in 81 cases [45 males and 36 females, aged (47.3±16.8) years].The incidence of unplanned reoperation was 2.4% (81/3 356). The most common primary diseases were retinal detachment (25 cases, 30.9%), proliferative diabetic retinopathy (23 cases, 28.4%) and silicone oil filled eye (17 cases, 21.0%). The most common reasons for unplanned reoperation were new onset or recurrent retinal detachment (33 times, 34.0%), increased intraocular pressure (23 times, 23.7%), as well as hyphema and inflammation (16 times, 16.5%). The percentages of the primary diseases and reasons for unplanned reoperation within 90 days following vitreoretinal surgery were not significantly different when compared with those during the primary admission. Desired results could be achieved in all cases after unplanned reoperation.

The primary diseases of unplanned reoperation for vitreoretinal surgery are complicated retinal detachment, diabetic retinopathy and silicone oil filled eyes. New onset or recurrent retinal detachment, increased intraocular pressure, hyphema and inflammation are common causes of reoperation.

To investigate the protective effect of liraglutide on kidney of diabetic mice induced by high-fat diet and its possible mechanisms.

C57BL/6J male mice were randomly divided into normal chow diet (NC) group and high-fat diet (HFD) group, which were fed with normal chow diet and HFD for 12 weeks respectively. After diet challenge, the mice were randomly divided into normal control group, normal chow diet with liraglutide treatment (NC+Lira) group, HFD group and high-fat diet with liraglutide treatment (HFD+Lira) group. The mice in NC+Lira and HFD+Lira groups were given intraperitoneal injection of liraglutide (400 μg·kg ^-1·d^-1) for 8 weeks, while mice in NC and HFD groups were given intraperitoneal injection of same amount of normal saline. Urinary albumin and creatinine levels were measured by enzyme-linked immunosorbent assay (ELISA). Renal morphology was observed by HE staining. The expression levels of silent mating type information regulation 2 homolog 1 (SIRT1) and thioredoxin-interacting protein (TXNIP) were determined by Western blot.

Compared with HFD group, liraglutide significantly lowered the body weight [(30.98±1.29) g vs (39.43±2.58) g], fasting blood glucose (FBG) [(7.21±0.15) mmol/L vs (9.55±0.29) mmol/L] and urinary albumin/creatinine ratio (ACR) [(205.48±17.14) μg/mg vs (319.86±34.14) μg/mg] in HFD+Lira group (allP<0.05). HE staining showed that glomerular hypertrophy of HFD group alleviated after liraglutide treatment. The expression level of TXNIP in the kidney of HFD mice significantly decreased after liraglutide treatment (0.41±0.10 vs 3.50±0.70), while expression level of SIRT1 significantly increased (0.75±0.15 vs 0.32±0.04) (both P<0.05).

Liraglutide could improve diabetic nephropathy by up-regulation of SIRT1 expression and down-regulation of TXNIP expression in diabetic mice induced by HFD.

To investigate the effect of fecal microbiota transplantation (FMT) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its regulatory mechanism.

Fifteen rats were divided into control group, LPS group and LPS+FMT group by random number table method. LPS group and LPS+FMT group were intraperitoneally injected with LPS to generate rat ALI model. After 24 h of modeling, feces (10 ml/kg) were given to the LPS+FMT group twice a day, and the control group and LPS group were given the same amount of normal saline. The intervention lasted for 2 days. After 24 h of the last fecal microbiota transplantation, arterial blood gas analysis was performed in each group. Then rats were sacrificed and enzyme-linked immunosorbent (ELISA) method was used to detect intercellular adhesion molecule 1 (ICAM-1) content in the serum and bronchoalveolar lavage fluid (BALF). The lung wet-dry weight ratio (W/D) was evaluated; HE staining and lung tissue pathology scoring, immunohistochemical detection of nuclear factor-kappa B (NF-κB) predominate nuclear expression and expression of ICAM-1 of alveolar epithelial cells were conducted; Western blot was used to detect the expression of proteins related to the intracellular phosphatidylinositol kinase (PI3K)/protein kinase (AKT) signaling pathway. Samples of rat feces were collected and DNA was extracted. Polymerase chain reaction (PCR) products of the V3 and V4 regions of the 16S ribosomal RNA gene (16SrDNA) were sequenced at high throughput, and bioinformatics analysis was conducted on the microbial community based on the operational classification unit.

The lung W/D and lung histopathological score of the LPS group were significantly higher than those of the control group, while the arterial partial oxygen pressure (PaO₂) of the LPS group was significantly lower than that of the control group [(79.2±5.89 vs 95.2±2.77) mmHg, 1 mmHg=0.133 kPa](all P<0.05). The results of intestinal flora sequencing revealed that the diversity index of LPS group was significantly higher than that of the control group, while the lactobacillus of LPS group rats was significantly lower than that of the control group. The content of ICAM-1 in serum, BALF and its relative expression on the cell membrane in the LPS group was significantly higher than that in the control group [(8.64±0.87) vs (7.40±0.32) ng/L; (0.941±0.035) vs (0.739±0.079) ng/L; (0.250±0.010) vs (0.076±0.010)] (all P<0.05). Moreover, the relative expression levels of phosphorylated P65 (p-P65), p-PI3K and p-AKT nucleoprotein in the LPS group were significantly higher than those in the control group (4.89±0.27 vs 3.28±0.13, 0.265±0.030 vs 0.036±0.013 and 0.444±0.040 vs 0.109±0.016) (all P<0.05). The above injury effect was reduced after fecal fungus transplantation. The lung W/D and lung pathological score of LPS+FMT group were significantly lower than those of LPS group, and PaO₂ of LPS+FMT group was significantly higher than that of LPS group [(88.0±3.53) mmHg]. The results of intestinal flora sequencing revealed that the diversity index of LPS+FMT group was significantly lower than that of LPS group, and the lactobacillus genus of LPS+FMT group was significantly higher than that of LPS group. ICAM-1 in the blood serum ((7.44±0.46) ng/L), BALF (0.834±0.040) ng/L) and its relative expression on alveolar epithelial cell membrane (0.173±0.030), the relative expression of p-P65, p-PI3K and p-AKT protein of NF-κB in alveolar epithelial cells was down-regulated ((2.99±0.28, 0.090±0.013 and 0.206±0.018) in LPS+FMT group than those of LPS group, the differences were statistically significant (allP<0.05).

Fecal transplantation can alleviate lipopolysaccharide-induced acute lung injury in rats, and its regulatory effect may be related to inhibiting the activation of PI3K/AKT/NF-κB signaling pathway and reducing the expression of inflammatory factor ICAM-1.

This article reports the clinical diagnosis and treatment of a patient with nephrogenic diabetes insipidus onset in juvenile years. The patient had slight changes in urine test, persistent hypokalemia with intermittent increases in serum creatinine during the course of the disease, and no long-term history of special medication and evidence of autoimmune disease. Renal pathology showed chronic tubulointerstitial disease with acute tubular injury and ischemic renal injury. Whole-gene exon sequencing revealed two pathogenic mutations in NPHP4. This mutation can cause renal depletion disease. After symptomatic potassium supplementation and volume improvement treatment, the serum creatinine and serum potassium levels of the patient remained stable.

Metronidazole is anti-Helicobacter pylori (H. pylori) Commonly used drugs in the treatment, the adverse reactions are mild, mainly digestive tract reactions, occasionally peripheral neuritis, leukopenia, etc. This paper reports a case of anti-H. pyloriSerious adverse reactions caused by metronidazole allergy in treatment are rare and reported for the first time in China.

Male idiopathic hypogonadotropic hypogonadism (IHH) is a class of diseases caused by disorders in the secretion or action of congenital gonadotropin-releasing hormone (GnRH), resulting in pubertal underdevelopment and gametogenesis disorders. In the past, IHH was considered a lifelong disease, but recently, clinical observations have repeatedly found that after treatment, the gonadal axis function of a few patients can be spontaneously reversed, or it can relapse after reversal. Therefore, in the follow-up process of IHH treatment, it is necessary to regularly evaluate the autonomic function of gonadal axis dynamically and in real time according to clinical manifestations and sex hormone test results, so as to prevent excessive treatment and erroneous treatment.

Asthma is a heterogeneous disease characterized by chronic airway inflammation. Most asthmatic patients are treated with inhaled glucocorticoids and long-acting beta₂After receptor agonists, the disease was well controlled, but some patients still experienced repeated acute exacerbation and gradual deterioration of lung function due to poor response to hormones. In recent years, with the deepening of the understanding of the pathogenesis of asthma, biological targeted therapy has become a hot spot in asthma research. In this paper, the research progress of biologically targeted agents in the treatment of asthma is reviewed.