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Methylimidazole compounds are byproducts formed during the caramel-coloring process and are used in various cosmetics. In addition metronidazole is an antibacterial and anti-inflammatory drug commonly used in modern medicine and is used in cosmetics to treat acne in the short-term. The illegal addition of metronidazole during cosmetics production can result in residual 2-methylimidazole (2-MEI), which, along with 4-methylimidazole (4-MEI), is a class 2B carcinogen. Therefore, establishing efficient, accurate, and sensitive analytical techniques for analyzing methylimidazole compounds in cosmetics is an urgent objective. In this study, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining 1-methylimidazole (1-MEI), 2-MEI, and 4-MEI in cosmetics was developed. Cosmetics samples were extracted via ultrasonication in acetonitrile and purified using a mixed cation-exchange (MCX) solid-phase extraction (SPE) column, with subsequent drying under a stream of nitrogen and redissolution in acetonitrile. The resulting solution was then filtered through a 0.22 μm organic filter membrane for further testing. The analytes were separated using an XBridge ® shield RP 18 chromatographic column (150 mm×4.6 mm, 3.5 μm) and isocratically eluted with 20 mmol/L ammonium formate solution (containing 0.1% formic acid)-acetonitrile (98∶2, v/v). The target compounds were ionized by electrospray ionization (ESI) source, analyzed in multi-reaction monitoring (MRM) mode, and quantified using the external standard method, with the peak area of the quantitative ion and the mass concentration of the compound taken as the longitudinal and transverse coordinates, respectively. Matrix-matching working curves were also constructed. 1-MEI exhibited good linear relationships in the range of 5-200 μg/L, with correlation coefficients ( r 2 )≥0.9994, while 2-MEI and 4-MEI showed good linearities in the range of 2-100 μg/L with r 2 ≥0.9984. The three methylimidazole compounds exhibited limits of detection (LODs) and quantification (LOQs) of 10-30 μg/kg and 25-100 μg/kg, respectively. Under three spiked levels (LOQ, 2LOQ, 10LOQ), the recoveries of three methylimidazole compounds were 80.9%-107.9%, with relative standard deviations (RSDs, n =6) of 1.2%-12.8%. The practicability of the method was examined using 48 cosmetic samples; 4-MEI was detected in nine samples at contents of 26-1000 μg/kg, while two samples contained 240 and 267 μg/kg of 2-MEI, respectively. 1-MEI was not detected in any of the 48 samples tested. The developed method is simple, fast, and highly sensitive, and provides methodological support for assessing risks and monitoring the three methylimidazole compounds in cosmetics through screening.

Objective: To investigate the expression level and clinical correlation of microRNA-144/451 gene cluster ( miR-144/451 ) in different types of anemia., Methods: The peripheral blood of patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and diffuse large B-cell lymphoma (DLBCL) who had been diagnosed with anemia for the first time and after chemotherapy were collected. The expression levels of miR-144 and miR-451 were measured by RT-qPCR, and the correlation between the expression levels of miR-144 and miR-451 and routine laboratory indexes was analyzed by Spearman correlation analysis., Results: The expression levels of miR-144 and miR-451 in the peripheral blood of AA and MDS patients were significantly lower than those in normal controls (all P < 0.01). No statistical differences were observed in the expression level of miR-144 in three subgroups of DLBCL patients ( P >0.05), while the expression level of miR-451 in peripheral blood of three subgroups of DLBCL patients were significantly higher than those in normal controls (all P < 0.05). Correlation analysis showed that the expression levels of miR-144 and miR-451 in AA patients were positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) ( r =0.629, 0.574). There were no significant correlations between the expression levels of miR-144 and miR-451 and laboratory parameters in MDS and DLBCL patients., Conclusion: Different types of anemia disorders have varying levels of miR-144 and miR-451 expression, which is anticipated to develop into a secondary diagnostic and differential diagnostic indicator for clinical anemia diseases.

Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant ( P =0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference ( P =0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant ( P <0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant ( P <0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P >0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population ( P <0.01), imatinib treatment group ( P =0.044) and no imatinib treatment group ( P <0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS ( P =0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.

Implementation research is a discipline that attempts to promote the application of evidence-based interventions in different settings and populations by using various methods and measures. Implementation strategies are the central part of implementation research, and as the field of implementation science evolves, more and more implementation strategies have been developed to facilitate the application of evidence-based interventions in the real world. To help researchers better understand and apply implementation strategies, this study will introduce implementation strategies in three aspects: classification, selection and application, and report.

Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.

Objective: To evaluate the differences in clinical characteristics between different genders of Chinese patients with systemic sclerosis(SSc). Methods: The data of SSc patients registered in Chinese Rheumatism Data Center between August 2008 and June 2020 were retrospectively analyzed. Results: A total of 1 844 patients with SSc were enrolled in the study. The ratio of males to females was 289 to 1 555. The onset age was (48.6±13.7) years in males and (45.5±13.1) years in females( P< 0.001). Male patients represented shorter disease duration [2.0(0.0, 4.0)years vs.3.0(1.0, 7.0) years, P< 0.001],higher proportion of diffuse cutaneous SSc (dcSSc) [63.0% (182/289)vs.44.2%(688/1 555), P< 0.001]. Although more man patients experienced smoking [47.4%(137/289) vs. 1.7%(27/1 555), P< 0.001] and exposure to harmful environments [7.6%(22/289) vs. 2.1%(33/1 555), P< 0.001], there was no statistically significant difference in interstitial lung disease between male and female patients [69.3%(181/261) vs. 74.5%(1 085/1 457), P= 0.084].Otherwise, Raynaud's phenomenon [87.7% (1 364/1 555) vs.75.4%(218/289), P< 0.001], arthritis [11.1%(173/1 555) vs.6.9%(20/289), P= 0.032], gastroesophageal reflux disease [22.0%(342/ 1 555) vs.13.1%(38/289), P= 0.001], and leucopoenia [10.7(161/1 511)% vs. 6.1%(17/279), P= 0.019] were more common in female patients, but finger ulcer was less common [22.5%(350/1 555) vs. 30.4%(88/289), P= 0.004]. Antinuclear antibody(ANA) positivity rate [85.6%(1 310/1 531) vs. 78.6%(221/281), P= 0.003], anti-RNP antibody positivity rate [23.1%(342/1 479) vs.14.0%(38/271), P= 0.001], anti-SSA antibody positivity rate [28.2%(419/1 487) vs.13.9%(38/274), P< 0.001] were higher in female patients. Physician's global assessment(PGA) scores [1.4 (1.0, 2.0) vs. 1.0 (0.3, 1.6), P< 0.001] and modified Rodnan Skin Score(mRSS) [18.0 (9.5, 28.0) vs. 14.0 (5.0, 28.0), P= 0.003] were higher in males. Conclusion: Even though male SSc patients account for a small proportion, more extensive skin involvement, finger ulcers and higher PGA are manifested in males. Physicians need pay attention to these clinical disparities between different genders in SSc.

Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1∶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P =0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P =0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.

Objective: To investigate MAML2 gene rearrangement, gene fusion patterns, and the clinicopathological characteristics of primary pulmonary mucoepidermoid carcinoma (PMEC). Methods: Forty-six cases of primary PMEC from Fudan University Zhongshan Hospital and Fudan University Shanghai Cancer Center between 2017 and 2020 were collected. MAML2 gene rearrangement in all cases was detected by fluorescence in situ hybridization (FISH). In 20 cases, MAML2 fusion patterns were detected by targeted RNA sequencing (RNAseq). The relationship between MAML2 gene rearrangement, fusion patterns, clinicopathological characteristics, and prognosis was analyzed. Results: The average age of PMEC patients was 41 years (range 15-71 years); the ratio of male to female was about 1.1 ∶ 1.0. Most PMECs were low grade in histopathology with an early clinical stage (stageⅠ-Ⅱ).The overall positive rate of MAML2 gene rearrangement detected by FISH was about 80.4% (37/46), and the rate was higher in low-grade PMEC (91.7%, 33/36). Of the 20 cases detected by RNAseq, all the 19 FISH positive cases showed gene fusion, mainly CRTC1-MAML2 fusion (16/19), the other three cases showed CRTC3-MAML2 fusion (3/19), the break point of all the fusion patterns was CRTC1/3 (exon 1)-MAML2 (exon 2); No gene fusion was detected in the single FISH negative case; Compared with the MAML2 FISH negative patients, the PMECs carrying CRTC1-MAML2 fusion were more commonly found in patients age ≤ 40 years, maximum tumor diameter ≤ 2 cm, low histopathological grade and early clinical stage (all P <0.05); The three PMECs carrying CRTC3-MAML2 fusion gene were all female with early clinical stage; Univariate analysis showed that MAML2 gene rearrangement/fusion, onset age ≤ 40 years old, smaller tumor size, low histopathological grade, early clinical stage, no metastasis at diagnosis and surgical treatment were significantly correlated with overall survival ( P <0.05), but Cox regression analysis suggested that none of the above indicators were the independent prognostic factors for the survival of PMEC. Conclusions: The high incidence of MAML2 gene rearrangement in PMEC suggests that it is an important molecular diagnostic marker of PMEC. RNAseq confirms that CRTC1/3-MAML2 is the main fusion pattern in PMEC, suggesting that MAML2 fusion transcription may be an important driving factor of PMEC. MAML2 rearrangement/fusion and related clinicopathological characteristics are associated with good prognosis.

Objective: To prepare a chitosan-modified cationic nanoemulsion that could be used to prolong the residence time of nasal vaccines in the nasal cavity and improve the cellular uptake efficiency so as to enhance the immune efficacy of nasal vaccines., Methods: A nanoemulsion-based vaccine coated with chitosan was prepared, and the particle size, potential, antigen encapsulation efficiency, stability as well as cytotoxicity were examined. The uptake efficiency of vaccine on different cells and the residence time of vaccine in the nasal cavity were measured. Finally, nasal vaccine was administered on mice and the antibody levels in the serum and in the nasal lavage fluids of the immunized mice were examined., Results: The nanoemulsion-based vaccine had an average particle size of (167.2±0.75) nm, a polydispersity index (PDI) of 0.21±0.01, and an average potential of (13.7±0.85) mV. The encapsulation efficiency of antigen was 92.7%. The nanoemulsion-based vaccine had good stability and did not show obvious cytotoxicity in Madin-Darby canine kidney (MDCK) epithelial cells. The vaccine demonstrated relatively high cellular uptake of antigens on DC2.4 and MDCK cells at (49.7±3.45)% and (59.7±2.19)%, respectively. Besides, the cationic nanoemulsion also significantly increased the residence time of the antigen, and a considerable amount of nanoemulsion-based vaccine was found remaining in the nasal cavity 60 minutes after administration. Compared with free antigen and the nanoemulsion without chitosan modification, the chitosan-modified nanoemulsion vaccine induced higher systemic and mucosal antibody levels in mice after nasal immunization ( P <0.01)., Conclusion: The chitosan-modified nanoemulsion vaccine prepared in the study can enhance the immune efficacy of nasal vaccines, showing great potential to be used as a delivery carrier for nasal vaccines., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: Platelet-derived growth factor α (PDGFRA) -mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods: A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed. Results: Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P >0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P =0.046), but there was no significant difference in OS among patients with different risk grades ( P =0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P >0.05). Univariate Cox analysis showed that RFS was associated with gender ( P =0.010), tumor size ( P =0.042), mitotic count ( P =0.003), and the modified NIH risk stratification ( P =0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P =0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P =0.031). Conclusions: Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.

Objective: To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy. Methods: Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining. Results: Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. Conclusion: Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.

Objective: To evaluate the clinical application of bronchial washing fluid (BWF) in the detection of epidermal growth factor receptor (EGFR) gene mutation in lung cancer patients during diagnostic bronchoscopic procedure. Methods: Patients with suspected lung cancer lesions but failed to be identified as malignancy by rapid on-site cytologic evaluation (ROSE) were enrolled. Performed blocker PCR for EGFR mutation detection using the supernatant and cell pellet of BWF samples and compared the detective results to the EGFR mutation status detected using histologic tumor samples. Results: A total of 85 BWF and paired histological samples were collected at Fudan University Affiliated Zhongshan Hospital from October 2016 to June 2017. There were 46 male and 39 female, with a mean age of 61 years (range 30-87 years). Thirty-one patients had benign diseases and 54 patients had primary lung cancer. Among these 54 lung cancer patients, the diagnoses were made basing on bronchoscopic biopsy samples in 31 patients. The detection rate of EGFR gene mutation in BWF samples was 100.0% concordant with that using histological samples.Another 23 cases whose bronchoscopic biopsy failed to establish malignant diagnoses were further identified by other sampling methods including surgical resection, lung biopsy, etc. A total of 15 patients were identified as EGFR mutated type by pathologic detection or clinically effect assessment, and BWF could detect 11 of them, accounting for 11/15 of all cases. Overall, BWF had achieved an overall accuracy of 95.3% (81/85) comparing to paired tumor histologic samples. Conclusions: BWF is an effective complementary specimen to bronchoscopic biopsy samples in EGFR gene mutation detection in patients with suspected lung cancer lesion and negative biopsy results evaluated by ROSE during bronchoscopy.

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation ( P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions: HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

A pot experiment was carried out to test the effects of salt levels on root morphology as well as the relationship between root morphology and salt tolerance with four cotton cultivars (salt-sensitive cultivar CCRI45, weak salt-resistance cultivar XLZ17, moderate salt-resistance cultivar XLZ13 and salt-resistance cultivar CCRI35). Results showed that dry mass and K + /Na + ratio of cotton root and leaf were significantly reduced by salt stress. Dry mass of root and leaf and K + /Na + ratio of root of cultivars XLZ13 and CCRI35 were 69.3%-104.4%, 24.8%-45.3% and 25.0%-45.8% higher than those of cultivar CCRI45, respectively. Root development was significantly restrained by salt stress. Total root length, total root surface area and total root volume of cultivars XLZ13 and CCRI35 were 15.2%-85.8%, 12.0%-68.5% and 31.7%-217.8% higher than those of cultivar CCRI45, respectively. Furthermore, the length of fine and middle roots, root surface area and root volume of cultivars XLZ13 and CCRI35 in 0-10 cm soil layer were 27.2%-73.9%, 39.6%-74.3% and 99.0%-309.7% higher than those of cultivar CCRI45, respectively. Results from principal component analysis showed that the variations of specific root length, root length ratio at 0-10 cm soil layer and fine root length ratio at 0-10 cm soil layer among cultivars was significant. Specific root length, root length ratio at 0-10 cm soil layer and fine root length ratio at 0-10 cm soil layer were the main root characters to distinguish different salt tolerant cotton cultivars. Results from the stepwise regression analysis showed that specific root length, coarse root length, coarse root area, and coarse root volume at 0-10 cm and 10-20 cm soil layers, as well as fine root area and middle root ratio at 0-10 cm soil layer were sensitive to salt. Salt tolerant cultivar adapted to salt stress through increasing root length ratio, fine length ratio, and specific root length.

With 15 N isotope labeled maize straw in nylon net bags and buried in the wheat field at two N rates of 0 and 200 kg N·hm -2 , the effects of nitrogen application on the decomposition of straw dry matter and the release dynamics of carbon, nitrogen, phosphorus and potassium (C, N, P and K) after maize straw retention were investigated in the winter wheat-summer maize rotation system in Guanzhong Plain, Shaanxi, China. Results showed that N application did not affect the decomposition of the returned straw C and dry matter, but promoted the release of P and inhibited the release of N and K from straw during sowing to wintering periods of winter wheat. From the grain filling to the harvest of winter wheat, the decomposition of the returned straw and the release of N, P and K were not affected, but the release of straw C was significantly enhanced by N application. The release dynamic of straw C was synchronized with the decomposition of the dry matter, and the C/N of straw declined gradually with the extension of wheat growing. Until the harvest of winter wheat, the accumulative decomposition rate of straw dry matter was less than 50%, and the total straw C release rate was around 47.9% to 51.1%. The C/N ratio of the returned straw was decreased from 32.2 to 20.2 and 17.9, respectively at N rates of 0 and 200 kg N·hm -2 . From sowing to harvest of winter wheat, the net release of N, P and K from the straw was observed. The N release was 7.2-9.4 kg·hm -2 and 12.7%-16.6% of the total straw N, and the P release was 1.29-1.44 kg·hm -2 and 29.0%-32.4% of the total straw P, while a great deal of K was released quickly, with approximately 80% of the straw K released before wintering, 51.8-52.5 kg·hm -2 and 90.5%-91.7% of the total straw K released at wheat harvest. It was suggested that the K fertilizer application should be decreased for the winter wheat due to the great amount K release from the returned maize straw, and an extra amount of N and P fertilizer should be applied under the straw retention cropping system.

Objective: To investigate the relationship between single nucleotide polymorphism (SNP) of BARD1 gene and BRCA1 gene in epithelial ovarian cancer (EOC). Methods: Nineteen EOC patients with BRCA1 gene mutation and 50 EOC cases without BRCA1 gene mutation between January 2016 and October 2016 were collected, and all EOC were diagnosed by pathological method. BARD1 gene variants were detected by next generation sequencing (NGS). The SNP of BARD1 gene was analyzed by Pearson linear correlation. Logistic regression analysis was used to research the clinicopathologic features and BRCA1 gene mutation associated with BARD1 gene SNP. Pearson's chi-square test was used to analyze the association between BARD1 gene Val507Met, Arg378Ser and Pro24Ser with different clinicopathologic features and BRCA1 gene mutation risk. Results: (1) Eight BARD1 gene variants were found in 69 ovarian cancer patients, in which Val507Met, Arg378Ser and Pro24Ser were common variants, and the rate of mutation were all 54% (37/69). (2) There was a significant linear correlation among Val507Met, Arg378Ser and Pro24Ser (all P <0.01). (3) Obvious differences were found in Val507Met, Arg378Ser and Pro24Ser of BARD1 gene between BRCA1(+) and BRCA1(-) (all P <0.05) . (4) No differences were found between BARD1 gene Val507Met, Arg378Ser and Pro24Ser and the clinicopathologic features (all P >0.05), while obvious differences were found in BRCA1 gene mutation compared to the controls group. The risk of BRCA1 mutation in Val507Met and Arg378Ser were more evident in subjects with negative family history, positive menopause history, negative tubal ligation, onset age (≤60 years old) and sensitivity to platinum-based chemotherapy in EOC (all P <0.05), while Pro24Ser was only more evident in positive menopause history of EOC ( P <0.05). Conclusions: BARD1 Val507Met, Arg378Ser and Pro24Ser are the common genotypes, which are associated with BRCA1 mutation in EOC. The family history, menopause history, tubal ligation, onset age and sensitivity to platinum-based chemotherapy have effects on BARD1 SNP in the risk of BRCA1 gene mutation.

Objective: To systematically evaluate the efficacy of high-flow nasal cannulae oxygen (HFNC) in patients with respiratory failure., Methods: Computerized PubMed, Embase, Web of Science, the Cochrane Library, CNKI, CBM, VIP, Wanfang Database up to March 31st, 2017, all published available randomized controlled trials (RCTs) or cohort studies about HFNC therapy for patients with respiratory failure were searched. The control group was treated with face mask oxygen therapy (FM) or non-invasive positive pressure ventilation (NIPPV), while the experimental group was treated with HFNC. The main outcome measurements included endotracheal intubation rate, patient comfort, and the secondary outcome was in-hospital mortality. The quality of the literature was completed by two professionally trained evidence-based medical students, and meta-analysis was performed on quality-compliant literature. Funnel plot was used to analyze the publication bias., Results: A total of 17 articles were enrolled including 15 RCTs and 2 cohort studies. There were 3 909 patients enrolled, 1 907 patients in HFNC group, and 2 002 in control group (1 068 patients with FM, and 934 with NIPPV). Meta-analysis showed that HFNC had a significant advantage over FM in reducing the tracheal intubation rate of patients with respiratory failure [odds ratio (OR) = 0.51, 95% confidence interval (95%CI) = 0.29-0.89, P = 0.02], but there was no significant difference as compared with that of NIPPV (OR = 0.80, 95%CI = 0.54-1.17, P = 0.25). It was shown by pooled analysis of two subgroups that compared with FM/NIPPV, HFNC had a significant advantage in reducing tracheal intubation rate in patients with respiratory failure (pooled OR = 0.66, 95%CI = 0.47-0.94, P = 0.02). Compared with FM, patients with respiratory failure were more likely to receive HFNC for comfort [standardized mean difference (SMD) = -0.41, 95%CI = -0.56 to -0.26, P < 0.000 01]. There was no significant difference in hospital mortality between HFNC and FM (OR = 0.82, 95%CI = 0.55-1.24, P = 0.35) or NIPPV (OR = 0.66, 95%CI = 0.37-1.17, P = 0.16). The results of pooled analysis of two subgroups were still unchanged (pooled OR = 0.75, 95%CI = 0.54-1.05, P = 0.09). It was shown by the funnel analysis that there was a bias in the study of tracheal intubation rate in the literature, while the bias of patient comfort and hospital mortality was low., Conclusions: Compared with FM, HFNC could reduce the rate of tracheal intubation in patients with respiratory failure, but no difference was found as compared with NIPPV. Compared with FM, HFNC made patients more comfortable, and it was easier to be accepted and tolerated. However, there was no difference in hospital mortality among FM, NIPPV, and HFNC.

Objective: To investigate the clinical features, immunohistochemical and differential diagnosis of desmoplastic fibroblastoma. Methods: The clinical data and pathology features of 7 cases of desmoplastic fibroblastoma were collected and immunohistochemical study were carried out in all cases with a review of the literatures. Results: There were 2 males and 5 females, with age ranging from 31 to 71 years (average and mean age were 59 and 61 years, respectively). The tumors were located in extremities and abdomen (left toe and right toe, right foot back, left leg and right thigh, right forearm and left hepatic lobe). Clinically, the tumors presented as slow growing painless masses of long standing duration. Grossly, the tumors were well-circumscribed with firm, white to gray cut-off surface. Tumor size ranged from 1.2 to 4.0 cm in maximum diameter (average 3.0 cm). Microscopically, 2 cases were located in dermis, 4 cases were located in subcutaneous and 1 case was located in liver parenchyma. It was composed of spindle-shaped or stellate cells with a fibroblastic or myofibroblastic appearance, and sparsely scattered in densely fibrous or fibromyxoid background. There was small vascular component in tumor background. At high magnification, the tumor cells were medium size with abundant cytoplasm, and the nucleus were small and always with small nucleoli. In some cases, the tumor cells were slightly larger with enlarged nuclei, but without cellular atypical and mitosis. Immunohistochemical study showed that the tumor cells were strongly positive for vimentin, desmin, S-100 protein and CD34, but CKpan was negative. α-SMA showed focal positive in one case. Ki-67 index ranged from 1% to 2%. Four cases were followed-up (ranged from 11 to 21 months, average 16.5 months) and the patients had no recurrence after surgery. Conclusions: Desmoplastic firoblastoma is a rare soft benign tumor. The differential diagnosis includes other benign or low-grade fibroblastic/myofibroblastic lesions.

Cucurbitaceae wilt of different hosts could be caused by Fusarium oxysporum. To clear the genetic diversity and phylogenetic relationship of F. oxysporum isolates from different Cucurbitaceae hosts and regions, genomic DNA of ninety-five strains of F. oxysporum isolated from different hosts and different regions were amplified by sequence-related amplified polymorphism (SRAP) molecular markers. All strains could be uniquely distinguished with 238 polymorphism bands which generated 100% of polymorphic ratio with 19 selective primer pairs. On average, each primer pairs amplified 12.5 loci and 12.5 polymorphic loci. A total of 166 bands of F. oxysporum f. sp. momordicae (FOM) were amplified, among which 145 polymorphic bands generated 87.4% of polymorphic ratio. On average, each primer combination amplified 8.7 loci and 7.7 polymorphic loci. This indicated that genetic variation of F. oxysporum was extensive. The genetic similarity coefficient of F. oxysporum was 0.68-0.99, and the average indexes of Nei's genetic diversity and Shannon were 0.2390 and 0.3718, respectively. Ninety-five strains of F. oxysporum were divided into four formae speciales from bitter gourd, cucumber, watermelon and melon, when the genetic similarity coefficient was 0.74. In SRAP dendrogram all the FOM isolates were gathered into one phylogenetic branch with the genetic similarity coefficient ranging from 0.78 to 0.99. The average indexes of Nei's genetic diversity and Shannon indices were 0.1811 and 0.2750, respectively. This indicated that genetic diversity of FOM was abundant, and the classification of phylogenetic group was related to geographic origin to some extent.

Property and flavor theory of traditional Chinese medicine (TCM) is the core base for clinical treatment of diseases. However, few research about its chemical and biological characterization was performed. In this paper, network pharmacology was adopted to review patterns around the theory of TCM. “Xiaoke” prescription database, which combinations of herb medicines for diabetes therapy, was firstly built to explore prescription regularity and screen core paired-components. The prescription regularity and molecular mechanism of flavor composition were explored through the relationship of “drug-compound-target-pathway-function” by ChEMBL, CTD and KEGG datebase. As a result, the tastes of “Gan” (sweetish taste) and “Ku” (bitter taste) were the popular therapeutic flavor to regulate the disorder of glucose and lipid metabolisms. The mechanism of Xiaoke was summarized from representative traditional Chinese medicine partner “Zhimu-Huangbai” and “Huangqi-Gegen”. The key components of “Gan”, including saponins stimulated insulin secretion, improve insulin resistance and promote glucose utilization. The components of “Ku”, including flavonoids and alkaloids regulate inflammatory cytokines, promoted the utilization of glucose, improve endocrine and metabolism through MAPK, PI3K-Akt, PPAR signal pathway. The TCM therapeutic mechanism about “Xiaoke” was preliminarily summarized to clear “heat” by anti-inflammation and immunoregulation, to regulate glucolipid metabolism for removing the satiation of digestion, and to improve the utilization of insulin and diabetes complications for endocrine adjusting. The results demonstrate that therapeutic principle of TCM for “Xiaoke” is comprehensive via multi pathway. This study provides a new research method and strategy for exploring the mechanism of TCM for diabetes therapy.

Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t -tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found ( P >0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls ( t =-3.536, P =0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group ( r =0.494, P <0.01), and the same correlation as CEA and CA(199) group ( r =0.897, P <0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group ( P >0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type ( P <0.05). The multiple factors analysis showed that the high level of CA(125) was a independent risk factor of BRCA mutations in sporadic HGSOC ( P =0.007). Conclusion: The combination of CA(125) with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.

In recent years, the research object of traditional Chinese medicine(TCM) analysis has not just been limited to the common analysis technology, but focused on the key relationship between chemical ingredients and traditional functions, including Chinese material medica (CMM) attributes, chemical substance and biological function. Near infrared spectroscopy (NIR) analysis technology, due to its unique advantages, has been developed rapidly in the field of pharmaceutical analysis, especially in the TCM analysis. NIRS can reflect the global chemical information comprehensively, and this holistic approach can be used for the identification and cluster analysis of CMM. On the other hand, inspiring by the concept of TCM quality markers (Q-markers), by means of the activity screening assay of the key components from the CMM, multiple bioactive components quantitation can be achieved by the NIRS combined with chemometrics. Taking the full advantage of the NIR technology, a simple and reliable method for the fast evaluation of the quality of TCMs can be provided. Therefore, the progress and trend of modern TCM quality evaluation by NIR are discussed and prospected in the present review., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Yuqiao Reservoir, an important adjusting reservoir in the project of diverting water from the Luanhe River to Tianjin City, is an important water resource for Tianjin City. Concentrations and spatial variation characteristics of Cd, As, Pb, Cu, Cr, and Zn from 33 sub watershed sampling sites of Yuqiao reservoir and the relationship to landscape pattern were discussed. The result showed that average concentrations of Cd, As, Cu, Cr in suspended particulate matter were higher than Chinese environmental quality standard Grade one for soils, and there were ecological risks for them because they could arrive at Yuqiao reservoir. The average concentrations of Cd, As, Pb, Cu, Cr, and Zn in surface sediments were 0.32 mg·kg -1 , 30.39 mg·kg -1 , 33.49 mg·kg -1 , 58.20 mg·kg -1 , 90.16 mg·kg -1 and 94.80 mg·kg -1 respectively. The average concentrations of Cd, As, Cu and the concentrations of Pb, Cr, Zn in partial samples exceeded Chinese environmental quality standard Grade one for soils. The average concentrations of Cd, Cr, Zn in surface sediments of three tributaries increased in the order of Linhe River >Shahe River >Lihe Rier, Cu decreased in the order of Linhe River < Shahe River < Lihe River, and As, Pb increased in the order of Shahe River >Linhe River >Lihe Ricer. Land use types in Yuqiao reservoir basin had some impact on the distribution of heavy metal concentrations in river surface sediments. Woodland and shrub grass land determined the natural distribution trend of heavy metals in surface sediments. Gardenland and industrial & mining land usage had impact on Cd, As, Pb, Cr distributions. Farmland and village & town land usage did not produce negative influence on heavy metal distribution.

Objective: An epidemiological survey was made on human intestinal protozoa in Xinjiang Uygur Autonomous Region (Xinjiang) to evaluate recent control achievements and provide basis for making specific control strategies., Methods: Regions in Xinjiang were categorized by types of ecological system and geographical characteristics into five ecological areas（types I-V） according to the National Ecological Function Stratification issued by the Ministry of Environment Protection and Chinese Academy of Science and Technology. Stratification sampling was made in each ecological area. Feces from human of all ages were collected for morphological identification of protozoan species using the Iodine Liquid Direct Smear Method., Results: In the five ecological areas, 26 886 people from 132 survey sites in 39 counties (cities) were examined, with an examination rate of 81.47% （26 886/33 000）. The infection rate was 0.32%（85/26 886）. Four species of intestinal protozoa were detected, i.e., Entamoeba histolytica, Giardia lamblia, Blastocystis hominis, and Entamoeba coli, with an infection rate of 0.22% （60/26 886）, 0.03% （9/26 886）, 0.01% （2/26 886） and 0.61% （17/26 886）, respectively. Of the five areas, the type IV area had the highest infection rate of 0.75%（28/3 758）（P<0.05）. Besides, the infection rate was higher in males （0.24%, 33/13 623） than that in females （0.39%, 52/13 263） （P<0.05）, higher in age ranges of 21-30（1.40%, 16/3 959） and 31-40 years（0.46%, 22/4 799） than other age groups （P>0.05）, higher in housewives （0.48%, 2/418） than those with other occupations, higher in the Hui group （0.61%, 15/2 445） than that in other ethnic groups, as well as highest in populations with a primary education level （0.37%, 35/9 375） and lowest in those with a college level or above（0.20%, 8/3 945）., Conclusion: The human intestinal protozoa infection was at a low level in Xinjiang in 2015.

Objective: To understand the hydatidosis prevalence in 6- to 12-year-old children in southern Xinjiang Uygur Autonomous Region and provide scientific basis for formulation of control measures., Methods: One primary school was selected from each of the pastoral area, pastoral-agricultural area, agricultural area, and township area in 42 counties （cities） of southern Xinjiang, using the stratified sampling method. With the consent of their parents, B ultrasonic abdominal scan and venous blood collection were performed on all the children （6-12 years） in the selected schools. Serum level of echinococcus antibody IgG was determined by ELISA. Hydatidosis prevalence and the serum level of IgG in these children were analyzed., Results: A total of 80 429 children were examined from 168 primary schools. B ultrasonic scan revealed hydatidosis in 9 children （0.01%）, comprising 3 cases in Kezhou, 2 in Aksu, 2 in Bazhou, and 2 in Kashi. ELISA results showed that 4 189 children were positive for serum IgG, with a positive rate of 5.21%. The positive rate was highest in Kashi （8.41%, 2 143/25 495）, followed by Aksu （5.69%, 913/16 051）, with significant difference between different areas （χ2=977.303， P<0.01）. The positive rate was lowest in 6-year children （2.13%, 44/2 065） and highest in 11-year children （5.68%, 822/14 462） （χ2=48.221, P<0.01）. In addition, the positive rate was highest in Uighur children（5.19%, 3 899/75 115）, followed by Mongolian children （4.27%, 68/1 592）, with no significant difference between ethnic groups （χ2=4.072, P>0.05）. Among the children of residents, children with a nomadic lifestyle, and children settled in winter and living in a nomadic lifestyle in summer, hydatidosis occurred in 7 residents and 2 children who settled in winter and living in a nomadic lifestyle in summer; and the positive rate of serum antibody was 5.45% （184/77 512）, 2.97% （3/101）, 0.07% （2/2 816）, respectively（χ2=148.609, P<0.01）., Conclusion: There is a low hydatidosis prevalence in 6- to 12-year-old children in southern Xinjiang, but the positive rate of serum echinococcus IgG in kashgar region, Uighur ethnicity, and children of the resident group are relatively high.

Objective: To understand the endemic status of echinococcosis in Xinjiang Uygur Autonomous Region, to provide scientific basis for planning and promoting control measures in this region. Methods Eight hundred people of all age ranges were examined in each of the selected agricultural area, pastoral area, pastoral-agricultural area, and township area of 92 counties in 14 prefectures in Xinjiang during March and October of 2012, resulting in a total of 3 200 people surveyed in each county. B ultrasonic abdominal scan was performed, accompanied by serum antibody detection for suspected cases., Methods: Eight hundred people of all age ranges were examined in each of the selected agricultural area, pastoral area, pastoral-agricultural area, and township area of 92 counties in 14 prefectures in Xinjiang during March and October of 2012, resulting in a total of 3 200 people surveyed in each county. B ultrasonic abdominal scan was performed, accompanied by serum antibody detection for suspected cases., Results: A total of 293 140 people were examined. The overall morbidity was 0.14%（407/293 140）. The morbidity in the north region was 0.18%（290/158 985, 71.25%of all the cases）, and that in the south region was 0.09%（117/134 155, 28.75% of all the cases）（P<0.05 between the regions）. The cases were mainly distributed in Urumqi City（19.90%, 81/407）, Tarbagatai Prefecture（13.27%, 54/407）, Yili Kazak Autonomous Prefecture（13.02%, 53/407） and Changji Hui Autonomous Prefecture（9.83%, 40/407）. The prevalence was higher in Mongolian［0.42%（21/5 045）］ and Kirgiz ［0.35%（32/9 045）］ than in other ethnic groups（0.07%-0.22%）（P<0.05）. There was no significant difference in prevalence between males［0.13%（195/144 715）］ and females［0.14%（212/148 425）］ （P>0.05）. The prevalence was lowest in the 0-9 year group［0.07%（7/10 754）］, and higher in the the age groups of 70-79［0.27%（33/12 310）］ and 80-99 years［0.28%（7/2 461）］, showing a trend of elevation with ageing. Further, the cases were mainly in the population of 30-49 years（43%, 175/407）. The prevalence was higher in the uneducated［0.25%, 39/15 470］ than in the educated populations（0.06%-0.14%）（P＜0.05）, and higher in pastoralists［0.29%, 63/22 074］ than in populations with other occupations（0.00%-0.13%）（P<0.05）. The prevalence in pastoral area, agricultural area, pastoral-agricultural area, and township area was 0.16%（70/44 247）, 0.16%（181/113 016）, 0.12%（88/70 610） and 0.10%（68/65 267）, respectively. The township area had the lowest prevalence, which was significantly different from both the pastoral area and the agricultural area (P<0.05)., Conclusion: Echincoccosis is widely distributed in Xinjiang, with more cases in the north.

Objective: To analyze the epidemiological characteristics of imported malaria in Xinjiang., Methods: The information of reported malaria cases and epidemiological records from various sources in Xinjiang Uygur Autonomous Region from 2004 to 2015 was collected. The epidemiological characteristics of malaria cases were analyzed., Results: Seventy-seven malaria cases were reported in Xinjiang from 2004 to 2015, and all were imported cases. In detail, 42 cases （54.5%） were reported during the time period of 2004-2009, with 24 laboratory diagnosed and 18 clinically diagnosed; 35 cases （45.5%） were reported from 2010 to 2015, with 27 laboratory diagnosed and 8 clinically diagnosed. Among the 51 cases with laboratory diagnosis, 18 were falciparum malaria, 31 were vivax malaria, and 2 unidentified. The male-to-female ratio was 6.7 ∶ 1（P<0.05）. The age range of the patients was 14-75 years （39.7 ± 13.3 years）, comprising 26.0% （20/77） for the range of 31-40 years and 24.7% （19/77） for the range of 41-50（P>0.05 among the age groups）. From the perspective of case sources, 28 cases （36.4%） were imported from Africa and 49 cases（63.6%） from Asia (including other provinces of China). The interval from onset to final diagnosis ranged 1-320 days. Only 3 patients（3.9%） were diagnosed within 24 h, and 59 patients（76.6%） were not diagnosed until or over one week. In addition, 28 cases（36.4%） were reported by medical institutions at the provincial level, 15 cases（19.5%） were reported by medical institutions at the prefecture level, 5 cases（6.5%） were reported by the Center for Disease Control and Prevention, and the rest 29 cases（37.7%） were reported at the county level or below. No secondary transmission was found., Conclusion: Most of the imported malaria cases during 2004-2015 were diagnosed with laboratory tests, reported by medical institutions, and were from Africa and Asia.

Objective: To understand the epidemiological characteristics of visceral leishmaniasis (VL) outbreak in Jiashi County of Xinjiang Uygur Autonomous Region in 2014, and provide basis for VL prevention and control strategies., Methods: Data on VL epidemic situation in Xinjiang from July 1, 2009 to June 30, 2015 were collected from Chinese CDC Infectious Disease Reporting Information Management System (reporting system). On-site epidemiological investigation was conducted in October, 2014, among children under 3 years in 23 villages in Gholtoghrak Township and Koxawat Township in Jiashi County, regions that had dramatically increased reports of VL cases from July 1. For suspected cases who showed symptoms such as fever and hepato-splenomegaly, blood (20 μl) was collected through fingerstick (with parental guardian consent) for rk39 immunochromatographic strip testing. Chil- dren with positive results were given sodium stibogluconate treatment (6x200 mg/kg, intravenously)., Results: A total of 637 VL cases were reported in Xinjiang from July 1, 2009 to June 30, 2015. Among the 192 cases reported from July 1, 2014 to June 30, 2015 in Xinjiang, cases from Jiashi County occupied 86.46% (166/192) of the cases. The number of VL cases in Jiashi County showed a trend of increase since the first report in August, with a total number of 114 in October, November and December. The 166 cases in Jiashi County had an age range of 23 days-8 years, with those under one year accounting for 95.18%(158/166). The 113 cases in Gholtoghrak Township of the County had an age range of 23 days-3 years, with those under one year accounting for 96.46% (109/113). The age--distribution of VL casess in the County accorded with the characteristic of the desert type. On-site investigation of 833 children in the 23 villiages revealed 11 children with positive results of rk39 immunochromatographic strip testing out of 14 suspected cases, all recovered after one course of sodium stibogluconate treatment., Conclusion: In 2014, VL outbreak occurs in Jiashi County with 95% of the cases being children under one year old. This outbreak was identified to be the desert type.

Unlabelled: [Abstract], Objective: To analyze the situation of echinococcosis surgerical cases in Xinjiang Uygur Autonomous Region from 2005 to 2013., Methods: The surgery cases of echinococcosis in Xinjiang from 2005 to 2013 were collected, and analyzed with SPSS 17.0 and Epi Info 3.5.3 software., Results: A total of 8 639 hydatid disease cases were reported during 2005-2013 from 94 counties (cities and districts) of 14 prefectures (municipalities) in the Region. The average number of annual operation cases were 960 cases (8,639/9 years), and the annual incidence was 4.40/100,000 (960/21.81 million). 82.8% (7,152/8,639) of report cases came from northern Xinjiang area with an incidence of 7.59/100,000, and 17.2% (1,487/8,639) distributed in southern Xinjiang area with an incidence of 1.58/100,000. There were 373 cases (4.4%, 373/8,639) reported in 2005, and increased to 1434 cases (16.5% 1,434/8,639) in 2013 (P<0.05). The cases mainly distributed in Yili Kazak Autonomous Prefecture (2,028 cases), Tarbagatai Prefecture (1,218 cases), Changji Hui Autonomous Prefecture (1,179 cases), and Urumqi City (1,128 cases) of the northern Xinjiang area. There were 4,557 male (52.8%, 4,557/8,639) and 4 082 famale patients (47.3%, 4,082/8,639)(P<0.05). The age distribution showed a single-peak curve, and more patients concentrated in the age group of 31-40 years, accounting for 26.2% (2,265/8,639). Among 8,639 cases, farmers accounted for 47.9% (4 134/8 639)., Conclusion: The nunber of surgical cases of echinococcosis increases every year in Xinjiang since 2005, and the distribution of the disease shows a trend from the agricultural and pastoral areas to the towns.

Crop growth is a continuous and dynamic process, and thus, the optimal meteorological indices for crop growth also change continuously. In this paper, the estimation algorithms of the daily available precipitation and the temporal interpolation methods of meteorological indices for crop growth were developed, and the climatic suitability model at daily scale was established, which was tested by the spring maize data of agro-meteorological stations in Northeast China. The simulated climatic suitability had significantly positive correlations with the height and 100-grain mass of spring maize. The correlation coefficient (R2) between the climatic suitability and the spring maize height was over 0.58 at vegetative growth stage, and over 0.45 at reproductive growth stage. The established climatic suitability model at daily scale could objectively reflect the interactions between crop growth and meteorological factors at vegetative growth stage and reproductive growth stage.

Objective: To apply moving percentile method on surveillance and early-warning on visceral leishmaniasis in Kashgar Region and evaluate its effect., Methods: Incidence data of visceral leishmaniasis in Kashgar Region were collected from the National Web-based Infectious Diseases Report System. Monthly detection was carried out by using moving percentile method. The 50th percentile (P50), 70th percentile (P70) and 90th percentile (P90) of historical baseline data were calculated for drawing a control chart, and P70 was adopted as the warning threshold to determine whether an epidemic would appear. If the number of cases in one month is higher than the corresponding P70 of historical baseline data, the warning signal will be generated. The sensitivity, specificity and positive predictive value were calculated for the evaluation of early-warning effect., Results: During the study period, 61.0% cases were reported in the year of 2008 and 2009, the incidence peak was from September to December, accounting for 51.9%, and infants under 3 years old were the population most threatened by visceral leishmaniasis, accounting for 62.7%. A total of 58 detections were performed, and 17 warning signals were generated by the threshold on P70. Among them, the numbers of cases in 9 detections were higher than the corresponding P90 of historical-baseline data. Based on the actually epidemic status of visceral leishmaniasis in study period, according to the threshold on P70, a total of 10 warning signals of 11 epidemics were detected, and the sensitivity of the warning model was 90.9% (10/11). 7 wrongly signals of 47 non-epidemics were detected, and the specificity was 85.1% (40/47). 10 of 17 signals were proved to be correct, and the positive predictive value was 58.8% (10/17)., Conclusion: The moving percentile method can effectively perform surveillance and early-warning on visceral leishmaniasis in Kashgar Region.

This study aims to clarify out the anti-inflammatory mechanism of Qingfei Xiaoyan Wan. Chemical constituents of Qingfei Xiaoyan Wan identified by UPLC Q-TOF, were submit to Molinspiration, PharmMapper and KEGG bioinformatics softwares for predicting their absorption parameters, target proteins and related pathways respectively; and the gene chip and real time-PCR were carried out to investigate the expression of inflammatory genes on lung tissue of guinea pigs or human bronchial epithelial cell lines. The predicted results showed that 19 of the 24 absorbable constituents affected at 9 inflammation-related pathways through 11 protein targets; Qingfei Xiaoyan Wan treatment can significantly reduce the infiltration of cytokines through ERK1 gene and 5 inflammatory pathways (Focal adhesion, Fc epsilon RI, Toll-like receptors, NK cell-mediated cytotoxic, and ERK/MAPK). The results of real time-PCR further confirmed that the anti-inflammatory effects of Qingfei Xiaoyan Wan were due to active ingredients such as arctigenin, cholic acid and sinapic acid intervened focal adhesion, Fc epsilon RI signaling and ERK/MAPK pathways. The novel approach of 'drug-target-pathway' will present an effective strategy for the study of traditional Chinese medicines.

Objective: Gastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs., Methods: Six GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples., Results: Direct comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR., Conclusions: The differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.

Objective: To investigate the clinical stage and histological grade of gastrointestinal stromal tumors., Methods: Twelve clinical and pathological parameters were assessed in 613 patients with follow-up information. These parameters were classified into two gross spread parameters including liver metastasis and peritoneal dissemination, five microscopic spread parameters including lymph node metastasis, vascular, fat, nerve and mucosal infiltration, and five histological parameters including mitotic count ≥ 10 per 50 high-power fields, muscularis propria infiltration, coagulative necrosis, perivascular pattern and severe nuclear atypia., Results: The accumulated 5-year disease-free survival (DFS) and overall survival (OS) of 293 patients without any of these predictive parameters of malignancy were 99.3% and 100.0%, respectively. They were regarded as nonmalignant and further evaluations on the stage and grade of these tumors were not performed. At least one and at most seven predictive parameters of malignancy were identified in 320 patients. For these patients, the accumulated 5-year DFS and OS rates were 43.9% (mean 6.7 years) and 59.7% (mean 9.3 years), respectively. The DFS showed significant difference between patients with and without gross spread (P < 0.01), with and without microscopic spread (P = 0.001). DFS and OS were associated with the number of predictive parameters of malignancy in patients without gross spread (P < 0.01 for both DFS and OS), but not in patients with gross spread (P = 0.882 and 0.441, respectively)., Conclusions: Malignant GIST could be divided into clinical stages I and II based on the absence and presence of gross spread, respectively. The degree of malignancy of patients in clinical stage I could be graded according to the number of predictive parameters of malignancy. Patients in clinical stage II were of the highest degree of malignancy regardless of the number of parameters. The staging and grading of gastrointestinal stromal tumors in this study are strongly associated with prognosis.

Objective: To explore the clinical significance of KRAS mutation detection in colorectal adenocarcinoma., Methods: Paraffin-embedded tissue specimens were obtained from 440 patients with colorectal adenocarcinoma. The genomic DNA was extracted. Mutations of exon 2 of KRAS gene were examined by PCR and direct sequencing., Results: Somatic mutations of KRAS gene were identified in 146 cases, with the mutation rate of 33.2% (146/440). Among these 146 patients, KRAS mutation involved codon 12 in 118 patients, including 35G > A (Gly12Asp, 62 cases), 35G > T (Gly12Val, 35 cases), 34G > T (Gly12Cys, 9 cases), 34G > A (Gly12Ser, 6 cases), 35G > C (Gly12Ala, 5 cases), and 34G > C (Gly12Arg, 1 case); in 27 patients the mutation involved codon 13, including 38G > A (Gly13Asp, 25 cases), 38G > C (Gly13 Val, 1 case) and 37G > T (Gly13 Cys, 1 case); and in one patient, the mutation involved codon 14 with 40G > A (Val14Ile). The status of KRAS or codon 12 mutations in colorectal adenocarcinoma was related to patients' gender (P = 0.021 and P = 0.030, respectively), and this significant correlation to females was conserved in clinical stage III (P = 0.007 and P = 0.003, respectively), but not in stages I, II, and IV. The status of KRAS or codon 12 mutations was also related to tumor stage. Between stage II and stage IV, the mutation rate of KRAS and codon 12 showed significant difference (P = 0.028 and 0.034, respectively). Between stage III and stage IV, only the codon 12 mutation rate showed significant difference (P = 0.011). Codon 13 mutation was not related to tumor stage., Conclusion: About one third of patients with colorectal adenocarcinoma have KRAS gene mutation, which might be related to patients' gender; and could be consistently detected by PCR and direct sequencing.

Objective: To investigate the clinicopathological and molecular genetic characteristics of gastrointestinal stromal tumor (GISTs) with significant cystic changes, and to assess their biological behavior., Methods: Clinicopathological features of 7 patients with cystic GISTs treated at the Zhongshan Hospital of Fudan University from February 2005 to January 2010 were summarized retrospectively. The mutations status of c-kit and PDGFR-α were analyzed., Results: There were 2 males and 5 females aged from 46 to 76 years old. Primary site of GISTs included stomach(n=4), duodenum(n=1), and small intestinal(n=2). Tumor size ranged from 6 to 16 cm with obviously cystic changes. Tumor cells were found in the solid components under microscope, of which epithelioid cell type were found in 4 case and spindle cell type in 3 cases. The mitotic figures were no more than 3/50 HPF in all the patients. According to the NIH criteria, 4 were high-risk and 3 were low-risk. Based on morphological characteristics, 3 cases were as borderline tumor, 3 moderate-risk, and 1 moderate-risk. Gene mutation of exon 11 of c-kit were identified in 3 cases. During the follow up ranging from 9 to 80 months, all the 7 patients had cancer-free survival., Conclusion: The biological behavior of cystic GIST is indolent with a low risk of malignancy and favorable prognosis.

Objective: To compare the effect of different models for the control of infectious source of schistosomiasis, so as to explore the control models suitable for lake and marshland regions., Methods: The models of "replacement of cattle with machine" and "grazing prohibition and establishing fixed pasture" were implemented in 2 towns of Gong'an and Jianli counties, Hubei Province, respectively, and the data of infection situation of human and livestock, Oncomelania hupensis snail situation and the contamination status of wild faeces were collected and analyzed from 2008 to 2010., Results: In 2010, for the model of "replacement of cattle with machine", the infection rate of residents in the observation group decreased by 56.82% comparing to that in 2008, the difference had a statistical significance (chi2 = 78.197, P < 0.01), and the decrease extent in the observation group was larger than that in the control group; the infection rates of cattle and snails, and the density of infected snails of the former were all decreased to 0. No wild faeces were discovered in the observation group, while 58 pieces of wild faeces were discovered but no schistosome eggs were found in these faeces in the control group. In 2010, for the model of "grazing prohibition and establishing fixed pasture", the infection rate of residents in the observation group decreased by 39.00% without a statistic significance (chi2 = 1.594, P > 0.05), and the infection rate of cattle decreased by 43.98% without a statistically significant difference (chi2 = 0.751, P > 0.05) comparing to those in 2008. The density of living snails decreased by 89.83% in the observation group, while that in the control group increased by 6.80%. A total of 11 pieces of wild faeces were collected in the observation group, with a positive rate of 18.18%, and 7 pieces were collected in the control group, all of which were negative. During the 2 years, no acute and advanced schistosomiasis patients were newly discovered., Conclusions: "Replacement of cattle with machine" and "grazing prohibition and establishing fixed pasture" are the main measures for schistosomiasis control in lake and marshland regions, the former is suitable for inner embankment regions, while the latter is suitable for the outer-embankment areas.