ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Objective The present study was conducted to identify the Vibrio cholera type and to analyze its antibiotic resistance in an epidemic of cholera in Haiyan County in 2018, which would provide the references for prevention and control of cholera. Methods Stool samples of the patient and his close contacts as well as the food and environmental samples were collected for identification of the type of Vibrio cholerae and the toxin gene. The resistance of identified Vibrio cholerae to 20 different common antibiotics were tested. Results A total of 176 samples were collected, including 101 stool samples from the case and his close contacts, 35 environmental samples and 40 food samples. Among those samples, only one strain of V. cholerae, O139, was isolated from the patient's first feces sample. It was detected as a toxin gene of ctxA positive by real-time fluorescence PCR. Antibiotic resistance test showed that the strain was sensitive to norfloxacin, levofloxacin, ciprofloxacin, cefotaxime, cephalothin, ampicillin, and amoxicillin. It was 100% resistant to tetracycline, doxycycline, neomycin, kanamycin, streptomycin, and rifampicin. Conclusion V. cholerae O139 strain with ctxA is detected in an epidemic of cholera. Norfloxacin, levofluoxacin and some other antibiotics could be used for clinical treatment and prevention. It should pay attention to this strain of V. cholera regarding the multiple drug resistance and the change of antibiotic resistance.

Objective: To investigate the clinical effects of Qinghuang powder, low-intensity chemotherapy and Qinghuang powder alternated with low-intensity chemotherapy in the treatment of elderly acute myeloid leukemia patients progressed from myelodysplastic syndromes (MDS-AML). Methods: A total of 32 elderly patients with MDS-AML treated in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2014 to December 2017 were retrospectively analyzed. Of them, 12 patients received Qinghuang powder (Qinghuang powder group), 6 patients received Qinghuang powder alternated with low-intensity chemotherapy (alternating group), and 14 patients received low-intensity chemotherapy (low-intensity chemotherapy group), based on the real world of patient's voluntary choice of treatment. The efficacy and adverse reactions in the 3 groups were observed. Results: The overall response number of Qinghuang powder, alternating, and low-intensity chemotherapy groups were 2, 2 and 4 cases, respectively, there was no significant difference among the 3 groups (P > 0.05). The median overall survival time of 3 groups were 14, 12 and 8 months, respectively, there was no significant difference among the 3 groups (P > 0.05). Two cases in Qinghuang powder group presented with gastrointestinal reactions; 3 cases in alternating group with myelosuppression, 2 cases with liver function damage, and 2 cases with gastrointestinal reaction; 11 cases in low-intensity chemotherapy group presented with bone marrow suppression, 3 cases with liver function damage, 7 cases with gastrointestinal reactions, and 2 cases with myocardial enzyme changes. The incidences of myelosuppression, liver function damage and myocardial enzyme changes in Qinghuang powder group were lower than those in the alternating group and low-intensity chemotherapy group. Conclusion The efficacy of Qinghuang powder or Qinghuang powder alternated with low-intensity chemotherapy for the treatment of elderly MDS-AML is not worse than the low-intensity chemotherapy, furthermore Qinghuang powder or Qinghuang powder alternated with low-intensity chemotherapy has fewer adverse reactions and better tolerance.

Objective: To investigate the diagnosis and treatment for enterocutaneous fistula (ECF) in China, and to explore the prognostic factors of ECF. Methods: A multi-center cross-sectional study was conducted based on the Registration System of Chinese Gastrointestinal Fistula and Intra-Abdominal Infections to collect the clinical data of ECF patients from 54 medical centers in 22 provinces/municipalities from January 1, 2018 to December 31, 2018. The clinical data included patient gender, age, length of hospital stay, intensive care unit (ICU) admission, underlying diseases, primary diseases, direct causes of ECF, location and type of ECF, complications, treatment and outcomes. All medical records were carefully filled in by the attending physicians, and then re-examined by more than two specialists. The diagnosis of ECF was based on the clinical manifestations, laboratory/imaging findings and intraoperative exploration. Results: A total of 1521 patients with ECF were enrolled, including 1099 males and 422 females, with a median age of 55 years. The top three primary diseases of ECF were malignant tumors in 626 cases (41.2%, including 540 gastrointestinal tumors, accounting for 86.3% of malignant tumors), gastrointestinal ulcers and perforations in 202 cases (13.3%), and trauma in 157 cases (10.3%). The direct causes of ECF were mainly surgical operation in 1194 cases (78.5%), followed by trauma in 156 (10.3%), spontaneous fistula due to Crohn′s disease in 92 (6.0%), radiation intestinal injury in 41 (2.7%), severe pancreatitis in 20 (1.3%), endoscopic treatment in 13 (0.9%) and 5 cases (0.3%) of unknown reasons. All the patients were divided into three groups: 1350 cases (88.7%) with simple ECF, 150 (9.9%) with multiple ECF, and 21 (1.4%) with combined internal fistula. Among the patients with simple ECF, 438 cases (28.8%) were jejuno-ileal fistula, 313 (20.6%) colon fistula, 170 (11.2%) rectal fistula, 111 (7.3%) duodenal fistula, 76 (5.0%) ileocecal fistula, 65 (4.3%) ileocolic anastomotic fistula, 55 (3.6%) duodenal stump fistula, 36 (2.4%) gastrointestinal anastomotic fistula, 36 (2.4%) esophagogastric/esophagojejunal anastomotic fistula, 29 (1.9%) gastric fistula and 21 (1.4%) cholangiopancreatiointestinal. Among all the simple ECF patients, 991 were tubular fistula and 359 were labial fistula. A total of 1146 patients finished the treatment, of whom 1061 (92.6%) were healed (586 by surgery and 475 self-healing) and 85 (7.4%) died. A total of 1043 patients (91.0%) received nutritional support therapy, and 77 (6.7%) received fistuloclysis. Infectious source control procedures were applied to 1042 patients, including 711 (62.0%) with active lavage and drainage and 331 (28.9%) with passive drainage. Among them, 841 patients (73.4%) underwent minimally invasive procedures of infectious source control (replacement of drainage tube through sinus tract, puncture drainage, etc.), 201 (17.5%) underwent laparotomy drainage, while 104 (9.1%) did not undergo any drainage measures. A total of 610 patients (53.2%) received definitive operation, 24 patients died within postoperative 30-day with mortality of 3.9% (24/610), 69 (11.3%) developed surgical site infection (SSI), and 24 (3.9%) had a relapse of fistula. The highest cure rate was achieved in ileocecal fistula (100%), followed by rectal fistula (96.2%, 128/133) and duodenal stump fistula (95.7%,44/46). The highest mortality was found in combined internal fistula (3/12) and no death in ileocecal fistula. Univariate prognostic analysis showed that primary diseases as Crohn′s disease (χ²=6.570, P=0.010) and appendicitis/appendiceal abscess (P=0.012), intestinal fistula combining with internal fistula (χ²=5.460, P=0.019), multiple ECF (χ²=7.135, P=0.008), esophagogastric / esophagojejunal anastomotic fistula (χ²=9.501, P=0.002), ECF at ileocecal junction (P=0.012), non-drainage/passive drainage before the diagnosis of intestinal fistula (χ²=9.688, P=0.008), non-drainage/passive drainage after the diagnosis of intestinal fistula (χ²=9.711, P=0.008), complicating with multiple organ dysfunction syndrome (MODS) (χ²=179.699, P<0.001), sepsis (χ²=211.851, P<0.001), hemorrhage (χ²=85.300, P<0.001), pulmonary infection (χ²=60.096, P<0.001), catheter-associated infection (χ²=10.617, P=0.001) and malnutrition (χ²=21.199, P<0.001) were associated with mortality. Multivariate prognostic analysis cofirmed that sepsis (OR=7.103, 95%CI:3.694-13.657, P<0.001), complicating with MODS (OR=5.018, 95%CI:2.170-11.604, P<0.001), and hemorrhage (OR=4.703, 95%CI: 2.300-9.618, P<0.001) were independent risk factors of the death for ECF patients. Meanwhile, active lavage and drainage after the definite ECF diagnosis was the protective factor (OR=0.223, 95%CI: 0.067-0.745, P=0.015). Conclusions The overall mortality of ECF is still high. Surgical operation is the most common cause of ECF. Complications e.g. sepsis, MODS, hemorrhage, and catheter-associated infection, are the main causes of death. Active lavage and drainage is important to improve the prognosis of ECF.

Objective To investigate the survival of oral arsenic-containing Qinghuang Powder (QHP) and low intensive chemotherapy (LIC) in the treatment of elderly patients with acute myeloid leukemia (AML).Methods Forty-two AML patients older than 60 years in Xiyuan Hospital from January 2015 to December 2017 were retrospectively analyzed.Of them,20 cases were treated with QHP (QHP group),22 cases were treated with LIC (LIC group).The survivals of the two groups were compared.Results There was no significant difference of median survival time (13 months vs.13.5 months,x2 =0.096,P =0.757),1-year survival rates (59.1％ vs.70.0 ％,x2 =0.543,P =0.461),2-year survival rates (13.6 ％ vs.15.0 ％,x2 =0.016,P ＞ 0.05),and 3-year survival rates (4.6 ％ vs.5.0 ％,x2 =0.005,P ＞ 0.05) between LIC and QHP groups.There was no significant difference of median survival time in age ≥75 year (12 months vs.12.5 months,x2 =1.317,P =0.251),performance status scores ＞ 2 (12 months vs.12 months,x2 =0.834,P =0.361),hematopoietic stem cell transplantation with combined disease index ＞ 2 (12 months vs.13 months,x2 =1.726,P =0.189),secondary AML (10 months vs.14 months,x2 =1.552,P =0.213),and poor cytogenetics (12 months vs.8 months,x2 =0.479,P =0.489) between LIC and QHP group.Conclusion The survival of elderly AML patients is considerable in patients treated with oral QHP and LIC,which suggests that oral QHP may be an equivalent alternative treatment since elderly AML (especially more than 75 years) patients refused to LIC therapy.

Objective: To analyze the gene mutations in the patients with myelodysplastic syndromes (MDS). Methods: Forty-seven patients with MDS newly diagnosed in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2016 to July 2017 were enrolled. NGS 127-gene panel was used to detect the gene mutations, and the relationship between the gene mutations and the clinicopathological features was also analyzed. Results: Thirty-one (66.0 %) cases had gene mutations in 47 patients with MDS, and 23 gene mutations were detected with clinical significances. There were 7 mutant genes with a mutation frequency over 5 % in the population, including U2AF1 (23.4 %), SF3B1 (12.8 %), ASXL1 (10.6 %), TET2 (8.5 %), BCOR (8.5 %), TP53 (8.5 %) and DNMT3A (6.4 %) in turn. Among 31 patients with gene mutations, 16 (51.6 %) patients had ≥ 2 synergistic mutations, and 12 cases had synergistic mutations in different genetic functional groups, which was higher than that in same genetic functional groups (4 cases). There was a tendency of coexistence in IDH2-KRAS, IDH2-SRSF2, IDH2-STAG2, KRAS-SRSF2, KRAS-STAG2, RUNX1-PHF6, EZH2-ASXL1, EZH2-ZRSR2, and NPM1-NRAS (all P < 0.05). The variant allele frequency (VAF) of signaling pathway related genes including JAK2, KRAS, NRAS, SH2B3 was low in general and in a sub-clone status. JAK2 gene mutation was observed in 1 case with MDS-U. SH2B3 gene mutation was observed in a patient with very poor prognosis of karyotype. SETPB1 and EZH1 gene mutations were observed in two patients with high-risk revised international prognostic scoring system (IPSS-R). Conclusions The common mutated genes include U2AF1, SF3B1, ASXL1 and TET2. The genes in different genetic functional groups tend to synergistic mutations. Gene mutations can be used to predict the prognosis of diseases and become the target in the treatment of MDS.

To analyze relative literatures about ectopic GH-secreting pituitary adenomas,its embryology,anatomic distribution,clinical and imaging features,diagnosis,treatment and prognosis.Ectopic GH-secreting pituitary adenomas is a rare disease.Its pathogenesis originates from defects of embryonic migration of pituitary.The most common position is in sphenoid sinus.Clinical features include placeholder effects of tumor,effects of growth hormone secretion,and intracranial pressure symptoms,et al.Treatments include surgical treatment,radiation therapy and drug therapy.

Objective: To construct the mutants of ARID1A gene, which is an important component in human chromosomal remodeling complex Switch/Sucrose Non Fermentable (SWI/SNF), and identify their overexpression in liver cancer HepG2 cells. Methods: Overlap PCR was used to construct domain truncated mutantss pcDNA6-ARID1A/ΔARID and pcDNA6-ARID1A/ΔD UF3518 based on wild type plasmids pcDNA6-ARID1A. Lipofectionmethod was used to transfect the wild type and mutants into HepG2. Real-time PCR and western blotting were used to confirm the overexpression of ARID1A and the mutants. Results: SDS-PAGE and sequencingresult confirmed the successful construction of pcDNA6-ARID1A/ΔARID and pcDNA6-ARID1A/ΔDUF3518. Real-time PCR and western blottingresult confirmed the overexpression of both mRNA and protein of wild type ARID1A and ARID1A/ΔARID. The mRNA levels indicated that ARID1A/Δ DUF3518 were overexpressed, but the protein levels were quite low. Conclusions Functional domain truncated mutants of ARID1A were successfully constructed. Overexpression of wild type ARID1A and ARID1A/ΔARID in liver cancer HepG2 cells was successful. Loss of ARID1A/ΔDUF3518 protein suggest that DUF3518 may contribute to the protein structure stability.

Background:Tryptophan(TRP)is an essential amino acid,and can produce 5-hydroxytryptamine(5-HT)via 5-HT signal pathway and kynurenine( KYN)metabolic pathway under the catalysis of enzyme,thereby participating in the pathogenesis of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome(IBS-D). Aims:To investigate the relationship between visceral sensitivity and TRP metabolic pathway in patients with IBS-D. Methods:Thirty patients with IBS-D and 30 healthy controls from June 2012 to January 2014 at Guangdong Provincial TCM Hospital were enrolled. Score of gastrointestinal symptom rating scale( GSRS)was evaluated. Visceral sensitivity was measured by anorectal manometry. RT-PCR and Western blotting were used to detect mRNA and protein expressions of colon mucosal IDo, respectively. Serum 5-HT,5-HIAA,TRP,IDo,KYN,KYNA concentrations and IDo activity,KAT activity were determined by high performance liquid chromatography assay. Results:Compared with control group,GSRS score was significantly increased(P < 0. 05),initial perception threshold,defecation threshold,pain threshold were significantly decreased(P < 0. 05),anorectal constriction pressure was significantly increased( P < 0. 05),serum 5-HT,5-HIAA concentrations were significantly increased(P < 0. 05),mRNA and protein expressions of IDo were significantly increased (P < 0. 05),serum KYN was significantly increased(P < 0. 05),KYNA was significantly decreased(P < 0. 01),IDo activity was significantly incseased(P < 0. 01),and KAT activity was significantly decreased in IBS-D group(P < 0. 01). Correlation analysis showed that initial perception threshold,defecation threshold,pain threshold and anorectal constriction pressure were correlated with 5-HT,5-HIAA,TRP,KYN,KYNA,IDo activity and KAT activity in patients with IBS-D (P < 0. 05). Conclusions:TRP metabolic pathway is correlated with visceral hypersensitivity in patients with IBS-D.

Objective To investigate the effects of intense low frequency noise on expression of caspase -3 in bama pigs ,and observe the death of cochlea hair cell .Methods 8 bama pigs were randomly divided into a normal control group(2 pigs) and experimental groups(6 pigs) .Auditory brainstem responses(ABR) were tested before the experiment .The control group was the same as the experimental groups except noise exposure .The experimental group was randomly divided into immediate group ,36 h group ,and 84 h group(2 pigs per group) .They were ex-posed to intense low frequency noise at 142 dB of 50 Hz for 5 min according to the three time points .ABR were test-ed again before the cochlea were collected at different time points .The expression of caspase -3 was studied through immunohistochemistry and immunofluorescence ,hair cell loss rate by counting to determine cell death .Results The average ABR threshold of 8 bama pigs(16 ears) before the exposure was 61 .25 ± 10 .72 dB nHL .ABR thresh-olds were not elicited after exposure to the noise .Different parts of bama pigs showed positive expression of caspase -3 in two ways .As time prolonged after exposure ,the positive expression of caspase -3 gradually weakened .The im-mediate group and 36 h group ,compared with the control group ,showed the apparent misplace of three out hair cells in the arrangement and levels .The 84 h group through immunofluorescence lost out hair cells ,and only inner hair cells were visible .Conclusion ABR thresholds were elevated after noise exposure .The procedure of hair cell nucleus damage and caspase-3 expression is different ,and the noise can induce opening apoptotic program of spiral ganglion .