Objective To analyze the clinical manifestations of refractory mycoplasma pneumoniae pneumonia (RMPP)which unresponded to methylprednisolone in the dosage of 2 mg·kg-1 ·d-1 for 3 day.Methods Retrospective analysis was performed on the clinical data of 120 children with RMPP.The patients were divided into effective group and ineffective group according to ini-tial effeet of 2 mg· kg-1 · d-1 methylprednisolone.The elinical manifestations,laboratory examination,radiological features and bronchofibroscopic findings of the children were compared.Results Twenty-eight patients in 120 were poor curative effect after regular 2 mg·kg-1 ·d-1 methyl prednisolone therapy,accounted for 23.3%.There were 10 patients in 28 with mixed infection,ac-counted for 35.7%;13 patients with appeared necrotizing pneumonia,accounted for 46.4%;13 patients with secretion obstruction, accounted for 46.4%;10 patients with endometrium necrosis,accounted for 35.7%.92 patients in 120 were good curative effect af-ter regular 2 mg·kg-1 ·d-1 methyl prednisolone therapy,accounted for 76.7%.There were 5 patients in 92 with mixed infection, accounted for 5.4%;10 patients with secretion obstruction,accounted for 10.9;5 patients with secretion obstruction,accounted for 5.4%.The difference was statistically significant (P <0.05).There were correlation between effect of hormone therapy and the levels of WBC,N,hs-CRP,LDH,PCT,IL-6,IL-8,LP,SF,D-dimmer.Multiple factors analysis showed that N,hs-CRP,LDH,IL-8, IL-6 were independent risk factors influence the effect of regular hormone therapy (P <0.05).The effective were improved after in-creasing hormone doses or share ivig.Antibiotic use days in effective group was obviously lower than that in ineffective group,.The difference was statistically significant (P <0.05).Duplex control antibiotics use ratio in ineffective group was significantly higher than that in effective group.The difference was statistically significant (P <0.05).Conclusion Treatment with 2 mg·kg-1 ·d-1 methvlprednisolone could improve clinical symptoms and radiological manifestations of most children with RMPP quickly.But it may be ineffective in some situations such as N,hs-CRP,LDH,IL-8 and IL-6.

Colorectal cancer is one of the common malignant tumors and the overall prognosis is poor. The search for a more effective treatment for colorectal cancer has never stopped. The current interaction between the modulated immune system and the tumor microenvironment is a hot topic in the treatment of colorectal cancer. The achievements involve immune checkpoint inhibition, cytokine therapy, toll?like receptors and autologous cell therapy. It has been proved that these methods have mild effect on tumor loading reduction. However, significant breakthrough has been achieved with the use of checkpoint inhibitors targeting cytotoxic T lymphocyte associated antigen?4 (CTLA?4),programmed death?1 (PD?1) and programmed death receptor ligand 1 (PD?L1). Immunotherapy is promising in the treatment of patients with refractory tumors. The success of this current immunotherapy approach is largely limited to tumors with high mutation amplification, such as melanoma,renal cell carcinoma ( RCC) and non?small cell lung cancer. However,this discovery has led the development of checkpoint inhibitors in the treatment of colorectal cancer with highly mutated amplification of mismatch repair gene to a new era.

Objective To investigate the diagnosis and treatment of solid-pseudopapillary tumor of pancreas (SPTP). Methods The clinical manifestations, imaging findings, treatment and prognosis of 36 patients with SPTP from September 2005 to December 2015 were retrospectively analyzed. Results All patients were female, with the average age of 30.5 years. There were 11 cases of abdominal mass and 15 cases of abdominal tenderness. Thirty-three patients underwent ultrasonography, which showed pancreatic solid heterogeneous hypoechoic, echogenic light clusters or cystic mixed echogenic masses;the tumors boundary were clear, and some tumors were separated in the center; most tumors were not accompanied by pancreatic duct and bile duct dilatation. CT plain scan showed that most tumors were single circular mixed density shadow with clear capsule;CT enhanced scan showed that the arterial phase of the cyst wall and solid area was mild or moderately enhanced, and the portal phase and the delayed phase continued to strengthen, and the cystic part was not strengthened in each period. All patients underwent surgical treatment. Postoperative pancreatic fistula occurred in 8 cases, edematous pancreatitis in 6 cases, incision infection in 2 cases, all of which were cured after symptomatic treatment. The patients were followed up for 5 to 120 months with an average of 56 months. All patients were not treated with postoperative radiotherapy or chemotherapy. Thirty-four patients had a good prognosis and no signs oftumor recurrence and metastasis;1 patient died of acute leukemia 2 months after discharge, and 1 patient was lost in follow-up after 1 year of postoperative liver metastasis. Conclusions The main patient group of SPTP is young women. The clinical symptoms are mostly abdominal mass and tenderness. Preoperative diagnosis is difficult. Imaging examination is great significance for the preoperative diagnosis of SPTP. Surgical resection is the only effective treatment. The choice of surgery should be based on the location of the tumor, the invasion tendency of the tumor seen during surgery, and the rapid pathology of the operation. Most patients with SPTP have a good prognosis, and the recurrence rate and metastasis rate are low.

Objective:To explore the effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis.Methods:(1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK-49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF-β1) was applied in the NRK-49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group ( n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results:(1) After NRK-49F cells were stimulated by TGF-β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF-β1 group and TGF-β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF-β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α-SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α-SMA were lower in the TGF-β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group ( P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α-SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions:CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.

Objective The aim of this study was to investigate the methylation status of fragile histidine triad( FHIT) gene, human mutl homolog 1(hMLH1)gene,p16 gene,retinoic acid receptor beta( RAR-beta) gene,Reprimo gene and tissue inhibitor of metalloproteinase 3 ( Timp3) gene in gastric cancer and corresponding paracancerous tissues. Methods The methylation levels of FHIT,hMLH1,p16,RAR-beta,Reprimo and TIMP3 genes in 42 clinically resected gastric cancer specimens and 42 corresponding paracancerous tissues were detected by sodium bisulfite sequencing. Results The average methylation rates of the genes in gastric cancer and corresponding paracancerous tissues were:FHIT(1. 50% ,1. 36% ),hMLH1(4. 77% ,0. 48% ),p16(9. 63% ,10. 36% ), RAR-beta(4. 75% ,4. 17% ),Reprimo(9. 71% ,3. 76% )and TIMP3 genes(18. 34% ,14. 06% ). Compared with the paracancerous control group,the average methylation rate of Reprimo gene was only statistically different in gastric cancer patients(P=0. 00787). The difference in methylation rate of Reprimo gene promoter in gastric cancer patients with the degree of tissue differentiation was sta-tistically significant(P<0. 05). Conclusion There has methylation in the cytosine guanidine dinucleotide island of the Reprimo gene promoter region in gastric cancer. The high methylation rate of the Reprimo gene can be used as a potential biomarker for gastric cancer to detect the early stage of gastric cancer.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.