Objective To analyze the spatial distribution of Helicobacter Pylori (Hp) infection and its correlation with gastrointestinal tumors in the physical examination population of Xi'an city, and to provide reference for the prevention of gastrointestinal tumors in this area. Methods A total of 23 200 subjects who underwent physical examination in 25 public hospitals in Xi'an from January 2019 to January 2023 were selected as the research objects. The basic Information of the patients was derived through the Hospital Information System (HIS), and all subjects underwent 13C-breath test and gastroenterological endoscope. ArcGIS 10.6 software was used to draw a statistical map of Hp infection in Xi 'an for spatial autocorrelation analysis. Hp infection in patients with different gastrointestinal tumors was analyzed. Results In this study population, there were 10 858 cases of Hp infection , with an infection rate of 46.80% ; among them , 5 491 cases were male, with an infection rate of 46.60% , and 5,367 cases were female, with an infection rate of 47.01% , and there was no significant difference in the infection rate between genders (P>0.05). The prevalence of HP infection was higher in the 30-year-old and 20-year-old groups, 55.62% and 42.71%, respectively, and the infection rate showed a first increase and then a decreasing trend with age (χ²_trend = 6201.21, 6945.22 , P<0.001 ). The spatial distribution of Hp infection rate in the physical examination population of each administrative region county in Xi'an was globally spatially positively correlated, with spatial clustering (Moran's I=0.14, P=0.02). Local spatial autocorrelation showed that the five districts and counties presented high-high clustering. A total of 418 cases of gastrointestinal tumors were detected, with a detection rate of 1.80% , including 156 cases of gastric cancer , 85.90% of Hp infection rate, 106 cases of gastric mucosa-associated lymphoid tissue lymphoma, 83.02% of Hp infection rate, 98 cases of colon cancer, 80.61% of Hp infection rate, 58 cases of rectal cancer, 84.48% of Hp infection rate, and the differences were statistically significant (χ²=13.49, 16.16, 17.27, 24.66, P<0.05 for all). Conclusion The distribution of Hp infection in the physical examination population of Xi'an city has the characteristics of spatial aggregation and is related to gastrointestinal tumor diseases. It is suggested to carry out Hp infection education for the population in key areas to prevent the occurrence of gastrointestinal tumor diseases.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Breast cancers that are positive for hormone receptor but negative for human epidermal growth factor receptor 2 (abbreviated as HR+/HER2-) account for approximately 60% of total cases. Targeting estrogen signaling is one of the most important therapeutic strategies for HR+/HER2- breast cancer. However, the management of endocrine-resistant HR+/HER2- breast cancer remains a difficult issue in clinical practice. Previous multi-omic analysis and translational research have identified the mechanisms underlying endocrine-resistance including genomic alteration and abnormal epigenetic modification. To overcome endocrine-resistance, we have established a comprehensive and coherent therapeutic strategy. In addition, several novel therapies have shown promising efficacy in previous clinical trials and will emerge as alternative options for targeting endocrine-resistant HR+/HER2- breast cancer. In this review, we will introduce the mechanisms of endocrine-resistance, explain the current therapeutic strategy for endocrine-resistant HR +/HER2 - breast cancer and discuss the possible targeted therapies in the future.

ObjectiveTo investigate the mechanism of protective effect of ethanol extracts of Hemsleya chinensis （HC-EE） on hydrochloric acid/ethanol （HCl/EtOH）-induced acute gastric ulcer in rats. MethodLipopolysaccharide （LPS）-induced RAW264.7 cells were used to evaluate inhibitory effect of HC-EE on the production of inflammatory mediators in vitro. A rat acute gastric ulcer model induced by HCl/EtOH （60% ethanol in 150 mmol·L^-1 HCl） was used to evaluate protective effect of HC-EE on acute gastric ulcer. Rats were divided into five groups， including normal group， model group， HC-EE low dose （HC-EE 30， 30 mg·kg^-1） group， HC-EE high dose （HC-EE 60， 60 mg·kg^-1） group and ranitidine （35 mg·kg^-1） group. For model and drug-treated groups， vehicle solvent or drugs were orally administered twice daily for 7 consecutive days before the rats were subjected to HCl/EtOH to induce acute gastric ulcer. After being anesthetized， ulcer surface of each rat was obtained and recorded using electronic imaging technology， and the ulcer inhibition rate was calculated by ImageJ 1.8.0. Hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining were used to observe the pathological histological changes in rats. Content of nitric oxide （NO） in cell culture medium was measured by the Griess method. The levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-6， vascular cell adhesion molecule-1 （VCAM-1） and prostaglandin E₂ （PGE₂） in rat serum （or cell culture medium） were determined by enzyme linked immunosorbent assay （ELISA）. The protein expressions of phosphorylation （p）-p38 mitogen activated protein kinase （MAPK）/p38 MAPK and p-nuclear transcription factor-κB （NF-κB） p65/NF-κB p65 in rat gastric tissue were detected by Western blot. ResultIn vitro assay showed HC-EE could significantly down-regulate the expressions of NO， TNF-α， IL-1β， IL-6 and VCAM-1 in LPS-induced cells （P<0.05， P<0.01）. In vivo experimental results showed that， compared with the normal group， gastric tissue of the model group was severely damaged， and the area of gastric ulcer was significantly enlarged， levels of TNF-α， IL-6 were significantly increased （P<0.01）， and the level of PGE₂ was significantly decreased （P<0.01）， the phosphorylation levels of of p38 MAPK， NF-κB p65 in gastric tissue were significantly increased （P<0.01）. Compared with the model group， HC-EE dose-dependently improved HCl/EtOH-induced gastric tissue injury and inflammatory cell infiltration， and it could increase ulcer inhibition rate， significantly decreased the release of TNF-α and IL-6 （P<0.01）， HC-EE 60 group could increase the content of PGE₂ （P<0.05）， and significantly inhibit the phosphorylation levels of p38 MAPK and NF-κB p65 （P<0.05， P<0.01）. ConclusionHC-EE can exert protective effect on HCl/EtOH-induced acute gastric ulcer in rats， and its mechanism may be related to the inhibition of expression of inflammatory mediators mediated by p38 MAPK/NF-κB signaling pathway.

Objective: To explore the prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) after surgical resection and establish a nomogram for survival prediction. Methods: A total of 160 patients with ICC who underwent surgical resection in the First Affiliated Hospital of Xi′an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed. Among them, 89 patients were males and 71 were females, aged from 29 to 81 years with a age of (57.41±10.35) years. Observation indicators included: (1) The result of follow-up: postoperative survival. (2) The univariate analysis and multivariate analysis affecting postoperative patients′ prognosis. (3) The establishment and validation of nomogram model. The follow-up using outpatient and telephone was performed once every 3 months within 1 year postoperatively and once every 3-6 months after 1 year postoperatively up to August 1, 2019. The follow-up included liver function, CA19-9, upper abdominal ultrasound, CT or MRI. The overall postoperative survival time, end point of observation, was the date from the operation date to the follow-up date, or the date of death due to tumor recurrence and metastasis. The patients′ clinicopathological data was included in the prognostic factor analysis, the Kaplan-meier method and Log-rank test were conducted for the univariate analysis, the Cox proportional risk regression model was used for the multivariate analysis. The independent risk factors based on Cox regression model were screened to establish a nomogram for postoperative survival prediction. The patients were divided into the model group (n=112) for the establishment of survival nomogram and the validation group (n=48) for the assessment of predictive ability at a ratio of 7∶3, and the accuracy of nomogram in postoperative survival prediction was assessed by c-index. Measurement data with normal distribution were expressed with (Mean±SD). Measurement data with skewed distribution were described as M (range). Count data were expressed as cases and percentage. Results: During the follow-up period, all patients with ICC after surgical resection were followed up for a survival time of 20 months (2-111 months). 100 patients died of multiple organ failure caused by tumor recurrence and metastasis and 60 patients survived. The 1-, 3- and 5-year overall survival rates of patients were 63.3%, 30.0% and 19.6%, respectively. Univariate analysis showed that CA19-9, hepatolithiasis, number of tumor, range of liver resection, tumor differentiation, pathology type, tumor diameter, vascular invasion, TNM stage, lymphatic metastasis, satellite foci and surgical margin were the prognostic factors of ICC patients after surgical resection (HR=1.78, 1.97, 2.91, 1.89, 3.06, 2.86, 2.07, 1.94, 2.24, 1.95, 2.68, 2.00, 95%CI: 1.12-2.85, 1.22-3.16, 1.85-4.56, 1.26-2.85, 1.38-6.82, 1.31-6.25, 1.37-3.14, 1.07-3.51, 1.24-4.06, 1.26-3.01, 1.28-5.60, 1.11-3.59, P<0.05). Multivariate analysis showed that hepatolithiasis, number of tumor, range of liver resection, tumor differentiation (low differentiation) and pathology type were independent risk factors of ICC patients after surgical resection (HR=2.47, 2.37, 2.06, 5.52, 5.72, 95%CI: 1.39-4.38, 1.44-3.91, 1.25-3.40, 1.24-24.49, 2.31-14.17, P<0.05). The nomogram was established based on above five independent risk factors, the c-index value for postoperative survival of the model group and validation group were 0.71 (95%CI: 0.64-0.79) and 0.71(95%CI: 0.61-0.81), respectively. Conclusion A nomogram based on hepatolithiasis, number of tumor, range of liver resection, tumor differentiation and pathology type has better accuracy in postoperative survival prediction for patients with ICC.

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ² test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ²=288.60,P<0.01),N stage(χ²=68.10, P<0.01), vascular invasion(χ²=128.70, P<0.01)and neural invasion(χ²=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ²=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

Human Rhinovirus (HRV) is one of the most frequent cause of the human respiratory tract infection.HRV is traditionally associated with the benign common cold and it has now been demonstrated as a respiratory pathogen in lower respiratory tract diseases,such as pneumonia,children's wheezy disease,asthma exacerbation and chronic obstructive pulmonary disease (COPD) etc.Since the first HRV was discovered in 1956,now more than 150 serotypes were confirmed.HRV is considered the most common cause of upper respiratory tract infection.Nearly years-round advances in molecular methods have enhanced our understanding of the genomic structure of HRV,especially the newly discovered HRV-C,and it has been found that HRV is closely related to human acute lower respiratory infections.

Objective To investigate the clinical and molecular epidemiologic features of human rhinovirus (HRV) in children with acute lower respiratory tract infection (ALRTI) in Shanghai by detecting HRV from bronchoalveolar lavage fluid (BALF) .Methods One hundred and thirty-five BALF samples were collected from children with ALRTI at Children′s Hospital of Fudan University from January to June in 2014 . The specimens were tested by one-step real-time reversible transcription (RT )-polymerase chain reaction (PCR) for HRV .Gene fragments of VP4/VP2 capsid protein of the HRV genome were amplified and sequenced .The phylogenetic trees of HRV strains were drawn .Chi-square test was used for statistical analysis .Result Among these 135 samples ,6(4 .4% ) were HRV positive , including 4 positive for HRV-A and 2 positive for unknown genotype .The age of children with HRV positive was 8 months to 8 years ,including 5 cases ≤ 3 years old .The nucleotide homology within 4 HRV-A samples varied 76 .5% -100 .0% .These 4 HRV-A sequences were respectively compared with reference strains of HRV-A ,HRV-B and HRV-C in GenBank .The nucleotide homology varied 73 .1% -91 .7% ,57 .8% -66 .0% and 59 .0% -65 .0% ,respectively .Among 135 children with ALRTI ,124 were diagnosed with ordinary pneumonia including 4 (3 .2% ,4/124) HRV positive and 11 were diagnosed with severe pneumonia (with respiratory failure and/or heart failure) including 2 HRV positive .All children with HRV presented with fever and cough .Most of them (5/6) were co-infected with other pathogens .In 5 children with HRV positive ,the peripheral blood leukocyte counts were less than 10 × 109/L , neutrophil percentages were less than 0 .50 ,C-reactive protein was less than 8 mg/L and procalcitonin was less than 0 .05 μg/L .All the children were clinically cured .Conclusions The detection of HRV in BALF samples indicates that HRV is one of the pathogens in children with ALRTI in Shanghai and HRV-A is more common .Gene fragments of VP4/VP2 capsid protein of HRV pathogenic strains display a high degree of genetic variability .

Objective To summarize and analyse the clinical characteristics,diagnosis and treatment options of neuroendocrine carcinoma of gallbladder (GB-NEC).Methods The data of 10 patients with GB-NEC treated in our hospital between December 2007 and December 2012 were retrospectively analyzed and compared with the data of 377 patients with gallbladder adenocarcinoma.Results The 10 patients with GB-NEC accounted for 2.2％ (10/464) of all gallbladder cancers that were treated during the study period.The mean age was 59.0 ± 10.0 years,the ratio of male to female was 1 ∶ 4.All the 10 patients had low-differentiated small cell NEC,four patients were accompanied with an adenocarcinoma.Immunohistochemical examinations showed that the positive rates of CgA,NSE,Syn,EMA were 100％ (10/10),100％ (10/10),88.9％ (8/9) and 87.5％ (7/8),respectively.One,two and seven patients had a TNM grade Ⅱ,ⅣA,and ⅣB,respectively.Seven patients (70.0％) had N2 lymphatic metastases,which was significantly higher than the percentage in patients with gallbladder adenocarcinoma (128/377,34.0％ ; P ＜ 0.05).Two patients were treated with radical resection,while the other 8 patients were treated with palliative surgery.The 1-,2-,and 3-year survival rates of the patients with GB-NEC were 20.0％,10.0％,and 0,respectively.The median survival time was 92 days.In contrast,the 1-,2-,3-,and 5-year survival rates of the 377 patients with gallbladder adenocarcinoma were 32.7％,25.4％,21.3％,and 11.7％ respectively,and the median survival time was 180 days.Condusions GB-NEC was found mainly in aged females.The clinical presentations were mainly non-specific,and immunohistochemical examinations were needed for a definite diagnosis.GB-NEC is highly malignant,and local invasion and lymphatic metastasis could occur early.The short-term recurrence rate was very high.The prognosis of GB-NEC was poorer than gallbladder adenocarcinoma,while surgical resection combined with radiotherapy,chemotherapy and TACE increased the survival of these patients.

To screen an efficient recombinant Staphylococcus aureus protein A (SpA) for preparing matrix for affinity purification of immunoglobulin G (IgG), a genetic engineering approach was used to obtain monomer, two, three, four and five tandem repeats genes of the Z domain of SpA, then the genes were cloned into expression vector pET-22b and subsequently expressed in Escherichia coli BL21 (DE3). After induction with lactose, the target proteins were purified by Ni2+ affinity chromatography. The proteins with two, three, four and five tandem repeats of the Z domain were then coupled to CNBr-activated Sepharose 4B as an affinity chromatography matrix for affinity purification of human IgG. Furthermore, the differences in protein yield and IgG-binding capacity at different recombinant proteins were analyzed. The target proteins with monomer and tandem repeats of the Z domain had an effective expression in the genetic engineering bacteria. IgG could be specifically absorbed from human plasma by affinity chromatography. The protein yield and amount of IgG absorption of per mole protein could be improved by increasing the tandem repeats number of the Z domain. Compared with other tandem repeats, four tandem repeats of the Z domain exhibited more protein yield (160 mg/10 g wet cells) and higher level of IgG absorption (34.4 mg human IgG/mL gel). Therefore, four tandem repeats of the Z domain is more suitable for preparing matrix for affinity purification of IgG.
Adsorption ; Bacterial Proteins ; biosynthesis ; genetics ; Chromatography, Affinity ; methods ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Humans ; Immunoglobulin G ; isolation & purification ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; metabolism ; Staphylococcal Protein A ; biosynthesis ; genetics ; Tandem Repeat Sequences