The crosstalk between efflux pump and resistance gene mutation in Helicobacter pylori.

Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in Helicobacter pylori. Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.

Identifying Qingkailing ingredients-dependent mesenchymal-epithelial transition factor-axiation "π" structuring module with angiogenesis and neurogenesis effects.

OBJECTIVE: To explore the functional role of the drug-dependent mesenchymal-epithelial transition (Met)-axiation "π" structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia. METHODS: We used a Glutathione S-transferase (GST)-pull down assay, isothermal titration calorimetry assay, and other related methods to identify the relationships among Met, inositol polyphosphate phosphatase like 1 (Inppl1), and death associated protein kinase 3 (Dapk3) in this allosteric module. The biological effects of the modules of neurons generation composed of Met, Inppl1, and Dapk3 were measured through Western blot, apoptosis analysis, and double immunofluorescence labeling. RESULTS: The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex; Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region. Thus, we obtained a "π" structuring module considered a neural regeneration module. The biological effects of angiogenesis and neurogenesis modules composed of Met, Inppl1, and Dapk3 were also verified. CONCLUSION: The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.

Helicobacter pylori vaccine: mucosal adjuvant & delivery systems.

Vaccination, especially mucosal vaccination, is considered to be effective in the management of Helicobacter pylori infections. However, most antigens alone cannot induce immune responses when administered mucosally and need to be co-administered with adjuvants or delivery systems. The current research on the mucosal adjuvant and delivery systems of vaccine against H. pylori, including advantages and disadvantages, mechanisms and applications is discussed in this review. Mutants of cholera toxin (CT) and the heat labile enterotoxin of Escherichia coli (LT), CpG oligodeoxynucleotides, biocompatible and biodegradable polymers, and live attenuated bacterial vectors may be promising adjuvant and delivery systems for H. pylori vaccine.

Establishment of a nomogram prediction model for risk of COPD complicating pulmonary interstitial fibrosis / 重庆医学

Objective To analyze the influencing factors of chronic obstructive pulmonary disease(COPD)complicating pulmonary interstitial fibrosis,and to establish a nomogram prediction model.Methods The clinical data of 195 patients with COPD admitted and treated in this hospital from January 2019 to Feb-ruary 2021 were retrospectively analyzed.The factors possibly affecting the patients with COPD complicating pulmonary interstitial fibrosis were collected,and the patients were divided into 2 groups according to whether having pulmonary interstitial fibrosis.The independent risk factors were analyzed and screened by the multi-variate logistic regression.Then the nomogram prediction model was constructed.Results Among the includ-ed 195 cases of COPD in this study,there were 50 cases(25.64％)of complicating pulmonary interstitial fi-brosis.The univariate and multivariate logistic regression analysis results showed that the smoking history,duration of COPD,frequency of acute exacerbations onset,serum transforming growth factor β1(TGF-β1),basic fibroblast growth factor(bFGF)and angiotensin Ⅱ(AngⅡ)were the independent influencing factors of COPD complicating pulmonary interstitial fibrosis(P＜0.05).The nomogram model was constructed accord-ing to the results of multivariate analysis results,and the area under the receiver operating characteristic(ROC)curve was 0.956(95％CI:0.930-0.983),the average absolute error of internal verification by the Bootstrap method was 0.025,and the prediction model performance basically fitted the ideal model.Conclusion The nomogram model constructed by this study for predicting the pulmonary interstitial fibrosis in COPD patients has high accuracy and distinction degree.

[Evaluation of implementation effect of schistosomiasis control program in Jiangsu Province from 2010 to 2015].

OBJECTIVE: To evaluate the actual effect of the schistosomiasis control program in Jiangsu Province from 2010 to 2015. METHODS: A total of 67 schistosomiasis-endemic counties in 10 cities were selected, and a combination of retrospective investigation and on-site investigation was adopted to collect and record the epidemic data of the counties from 2010 to 2015, and a retrospective survey database of epidemic situation was established. The effects of integrated control strategies with both Oncomelania hupensis snail control and infection source control were evaluated. RESULTS: From 2010 to 2015, 2 465 911 persons who lived in endemic areas were detected for schistosomiasis, with 16 974 positive cases of blood examinations, and 8 positive cases of fecal examinations. Totally 5 145 people with advanced schistosomiasis were treated and 40 460 people with the history of schistosome cercarial-infested water contact received the expanded chemotherapy. A total of 127 636 cattle raised in the endemic areas were detected, and 51 619 cattle (head-times) with the history of cercarial-infested water contact also received the expanded chemotherapy. The area with snails control by molluscicides was 18 604.84 hm2. By the end of 2015, schistosomeinfected snails had not been found and there was no zoological schistosome infection for 5 consecutive years, and in addition, there had been no acute schistosome-infected persons for 6 consecutive years in the whole province. The area with snails dropped to 1 977.18 hm2, with a decreasing rate of 55.24% compared with that in 2010. CONCLUSIONS: After the implementation of the plan for the prevention and control of schistosomiasis in Jiangsu Province (2010-2015), the prevention and control of schistosomiasis has achieved remarkable effects and realized the goal of the plan.

Modulative effect of Physalis alkekengi on both gut bacterial and fungal micro-ecosystem / 中草药·英文版

OBJECTIVE@#Gut microbiome is an intricate micro-ecosystem mediating the human health and drug efficacy. Physalis alkekengi (PAL) is an edible and time-honored traditional Chinese medicine. Several pharmacological effects of PAL have been verified and gut bacteria are implied in its therapeutic actions. However, the detailed modulation of PAL on gut bacterial species and on gut fungi remains largely unknown. We, therefore, designed a preliminary experiment in normal mice to reveal the modulation effect of PAL on both gut bacteria and fungi, and explore the interaction between them.@*METHODS@#Herein, the aqueous extract of PAL was orally administrated to normal C57BL/6 mice for four weeks. The full-length 16S rRNA and ITS1/2 gene sequencing were explored to detect the taxa of gut bacteria and gut fungi after PAL treatment, respectively.@*RESULTS@#Oral administration of PAL notably enriched anti-inflammatory bacterial species such as Duncaniella spp. and Kineothrix alysoides, whereas decreased pro-inflammatory species such as Mucispirillum schaedleri. Simultaneously, PAL increased the abundance of gut fungi Aspergillus ochraceus, Cladosporium sp. and Alternaria sp., and decreased Penicillium janthinellum. Correlation network analysis identified two co-existing microbial groups (groups 1 and 2) that were negatively associated with each other. The group 1 comprised PAL-enriched bacteria and fungi, while group 2 was mainly normal chow-enriched bacteria and fungi. In group 1, Antrodia monomitica, Aspergillus clavatus, Mortierella kuhlmanii and Sarcinomyces sp. MA 4787 were positively correlated with Bifidobacterium globosum, Romboutsia ilealis and so on. In group 2, Chaetomium subspirilliferum, Septoria orchidearum and Cephaliophora tropica were positively related to Lactobacillus spp.@*CONCLUSION@#Altogether, this preliminary study first demonstrated the modulation effect of PAL on both gut bacteria and gut fungi, which may shed light on the elucidation of PAL's pharmacological mechanism.

Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy / 中华胃肠外科杂志

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

Integrated Metagenomics and UPLC-Q-TOF-MS/MS to Explore the Mechanism of Dexamethasone on Pneumonia in Rats / 中山大学学报(医学科学版)

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.

[Investigation of Toxoplasma gondii infection among special populations in Nanjing City, Jiangsu Province].

OBJECTIVE: To understand the prevalence of Toxoplasma gondii infection among special populations in Nanjing City, so as to provide the reference for formulating the interventions for the prevention and control of T. gondii infections in this population. METHODS: The HIV/AIDS patients, tumor patients, pregnant women, and people with livestock and poultry breeding or processing works were selected as the study subjects from September to November 2015. The venous blood samples were collected from each participant for detecting IgG and IgM antibodies against T. gondii by ELISA. RESULTS: The overall prevalence of T. gondii infection was 10.2% in the study subjects in Nanjing City. The T. gondii infection rates were 12.2%, 11.3%, 4.0%, and 13.0% among the HIV/AIDS patients, tumor patients, pregnant women, and people with livestock and poultry breeding or processing works, respectively, and there was no statistically significant difference among the four groups (χ2 = 5.668, P = 0.130). The prevalence of T. gondii infection was higher in men than in women (15.3% vs. 5.8%; χ2 = 10.213, P = 0.001), and there were significant differences in the prevalence of T. gondii infection in terms of gender (χ2 = 9.501, P = 0.023), education levels (χ2 = 9.850, P = 0.043) or occupations (χ2 = 8.983, P = 0.062). CONCLUSIONS: The infection rate of T. gondii among the special population in Nanjing City is high. Therefore, the health education intervention should be strengthened in the follow-up work for the special population.

[Analysis of human intestinal nematode infections in Nanjing City from 2006 to 2015].

OBJECTIVE: To analyze the epidemiological situation of human intestinal nematode infections in Nanjing City from 2006 to 2015, so as to provide the reference for formulating prevention and control measures. METHODS: The surveillance data of human intestinal nematode infections in Nanjing City from 2006 to 2015 were collected and analyzed statistically. RESULTS: From 2006 to 2015, 98 804 person-times of residents were surveyed in Nanjing City, and 465 person-times of residents were detected with intestinal nematode infections. The highest infection rate was in 2006 (1.97%), and the lowest in 2013 and 2015 (both 0.05%). Moreover, the positive rate of human intestinal nematode infections showed a significantly declining trend in total ( χ2 = 552.19, P < 0.001). Meanwhile, the numbers of Ascaris lumbricoides, hookworm and Trichuris trichura cases were 329, 98 and 25 respectively, and the infection rates were 0.33%, 0.10% and 0.03% respectively. Among them, 443 cases had mild infection intensity (98.66%). There were 462 cases of single-infection (99.35%), and 3 of co-infection of two parasites (0.65%). From 2006 to 2015, 92 539 person-times of children under 12 years old were surveyed for Enterobius vermicularis infection and 352 cases were detected with E. vermicularis infection. Moreover, the positive rate showed a significantly decreasing trend in total (χ2 = 147.94, P <0.001). CONCLUSIONS: The control effect of human intestinal nematode infections in Nanjing City is remarkable. However, the surveillance and health education in key groups still should be strengthened, and the prevention and control programs should be adjusted promptly to further consolidating the effectiveness of intestinal nematode disease prevention and control.

Evaluation of the effects of different 14C-urea breath test products in the diagnosis of Helicobacter pylori infection / 中华消化杂志

Objective:To evaluate the effects of the cassette 14C-urea breath test kit, scintillation sampling bottle (solid-state scintillation method) and liquid scintillation 14C-urea breath test kit in the diagnosis of Helicobacter pylori ( H. pylori) infection. Methods:From January 7 to October 28, 2020, 239 patients were enrolled who visited Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine and the First Affiliated Hospital of Nanchang University. All subjects first received 14C-urea breath test.Within >1 to <7 days after gas collection, mucosal tissues were taken under gastroscopy for gold standard test, including biopsy and rapid urease test (RUT). If both biopsy and RUT indicated H. pylori positive, the result of gold standard test was H. pylori positive, and if both were negative, the result of gold standard test was H. pylori negative. If the results of biopsy and RUT were inconsistent, they were not included in the subsequent analysis. Based on the results of gold standard test, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the cassette 14C-urea breath test kit, scintillation sampling bottle, and liquid scintillation 14C-urea breath test kit in the diagnosis of H. pylori infection were analyzed. The safety of the test was evaluated by whether there were any adverse events during the test. Descriptive methods were used for statistical analysis. Results:Among the 239 subjects, 12 cases did not complete the test, 227 subjects finally completed the test. The test completion rate was 95.0% (227/239). No.008 patient was only included in the analysis of cassette 14C-urea breath test kit and scintillation sampling bottle because of lacking the result of liquid scintillation breath test. The results of gold standard test showed that among 227 patients, 87 cases were H. pylori positive, 118 cases were H. pylori negative. The results of biopsy and RUT were inconsistent in 22 cases, so they were not included in the subsequent analysis. Excluding No.008 patient, the results of gold standard test showed that 86 cases were H. pylori positive and 118 cases were negative. Based on the results of gold standard test, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of cassette 14C-urea breath test kit, scintillation sampling bottle, and the liquid scintillation 14C-urea breath test kit in the diagnosis of H. pylori infection were 91.9%, 100.0%, 96.6%, 100.0% and 94.4%, respectively; 95.4%, 97.5%, 96.6%, 96.5% and 96.6%, respectively; and 96.5%, 99.2%, 98.0%, 98.8% and 97.5%, respectively. Only one adverse event (right upper abdominal pain after eating) occurred. Combined with the patients condition, the adverse event was determined as the onset of chronic cholecystitis and it might not be related to the test medication. Conclusions:Cassette 14C-urea breath test kit, scintillation sampling bottle, and liquid scintillation 14C-urea breath test kit have reliable performance, good safety, and high sensitivity, specificity and accuracy in the diagnosis of H. pylori infection, which are worthy of clinical application.

In situ activity analysis of two-step labeling probiotics with double fluorescent probes in intestinal tract / 药学学报

Effective supplementation of probiotics can be beneficial to intestinal health, but in situ analysis of probiotics activity has rarely been reported. In this study, by coupling fluorescein 5-isothiocyanate (FITC) and 5(6)-carboxytetramethylrhodamine N-succinimidyl ester (5(6)-TAMRA-SE) with D-lysine, two fluorescent D-amino acids (FDAAs) probes were obtained: green probe (fluorescein-D-lysine, FDL) and red probe (TAMRA-D-lysine, TDL). Then, we tried to label the three kinds of probiotics, Lactobacillus acidophilus (LA), Lactobacillus casei (LC) and Veillonella atypica (VA) in vitro. FDAAs was applied to the labeling of intestinal flora in mice, and a method was established to investigate the oral survival rate of three commonly used probiotics. All animal experiments were approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine. The results show that the two synthetic FDAAs can be non-toxic and 100% for the in vitro labeling of the three probiotics. Known by FDAAs two-step labeling of oral probiotics, the high survival rate of LA was 92.30% ± 1.67%. The survival rates of VA and LC are similar, 84.13% ± 4.06% and 82.27% ± 2.43%, respectively. This study can quickly compare the changes of colonization survival rate of different probiotics in vivo, provide theoretical support for the in situ colonization activity of probiotics in the intestine, and guide the rational drug use of clinical probiotics.

[Endemic situation of schistosomiasis at national surveillance sites in Nanjing City, 2015].

OBJECTIVE: To understand the dynamic endemic situation of schistosomiasis in Nanjing City, 2015, so as to provide evidences for policy-making of schistosomiasis control. METHODS: According to The National Scheme of Schistosomiasis Surveillance (2014), the endemic situation of schistosomiasis was monitored in 11 national surveillance sites in Nanjing. RESULTS: The positive rates of serological (IHA) and stool examinations were 2.97% (97/3 269) and 0 for local residents, and 0.52％ (12/2 298) and 0 for migrant people, respectively. No schistosome-infected livestock was found. Totally 147.295 3 hm2 area with Oncomelania hupensis snails were found, but no schistosome-infected snails were discovered. CONCLUSIONS: The endemic situation of schistosomiasis declines greatly in Nanjing City in 2015. However, the control work still should be strengthened to consolidate the achievements of schistosomiasis control.

[Epidemiological analysis of malaria prevalence in Nanjing City from 2010 to 2015].

OBJECTIVE: To analyze the epidemiological characteristics of malaria in Nanjing City, so as to provide the evidence for further formulating and adjusting the malaria prevention and control strategy. METHODS: The data of malaria situation, malaria cases and epidemiological investigations were collected from the Internet Reporting System in Nanjing City from 2010 to 2015 and analyzed statistically. RESULTS: A total of 137 confirmed malaria cases were reported in Nanjing City from 2010 to 2015, including 102 falciparum malaria cases (74.45%), 33 vivax malaria cases (24.09%), one ovale malaria case (0.73%) and one quartan malaria case (0.73%). Among the 137 malaria cases, 126 cases (91.97%) were imported from foreign countries, 2 cases (1.46%) were infected locally, and nine cases (6.57%) were imported from other provinces in China. Among the 126 overseas imported cases, 117 cases were imported from African countries and 9 from Asian countries. These malaria cases were majorly young men working as migrant workers, laborers and technical persons. About 19.30% of the cases went to hospital on onset day, and 55.65% were confirmed by medical institutions as malaria in the same day. The majority of diagnosis institutions were municipal hospitals (74.45%). CONCLUSIONS: The number of malaria cases in Nanjing City is declining year by year. The local infections are eliminating gradually. However, the situation of imported malaria from overseas is still serious. Therefore, the surveillance work and health education still should be strengthened, so as to reduce the risk of imported malaria.

Epidemic situation and diagnosis of imported malaria before and after malaria elimination in Nanjing City, Jiangsu Province / 中国血吸虫病防治杂志

Objective To analyze the epidemiological characteristics and diagnosis of imported malaria before and after malaria elimination in Nanjing City of Jiangsu Province, so as to provide the scientific evidence for formulating the malaria control strategy after malaria elimination. Methods Data pertaining to the epidemic situation and individual investigation of malaria in Nanjing City before (from 2012 to 2016) and after malaria elimination (from 2017 to 2020) were captured from the National Notifiable Communicable Disease Reporting System and the Information System for Parasitic Diseases Control and Prevention and were analyzed statistically. Results A total of 178 malaria cases were reported in Nanjing City from 2012 to 2020, and all were imported cases. There were 99 malaria cases reported before malaria elimination in Nanjing City, including 78 cases with Plasmodium falciparum malaria (78.79%), 5 cases with P. vivax malaria (5.05%), 10 cases with P. ovale malaria (10.10%), 3 cases with P. malariae malaria (3.03%) and 3 cases with mixed infections (3.03%), and 79 malaria cases reported after elimination, including 63 cases with P. falciparum malaria (79.75%), 5 cases with P. vivax malaria (6.33%), 9 cases with P. ovale malaria (11.39%), 2 cases with P. malariae malaria (2.53%). There was no significant difference in the proportion of each type of malaria cases in Nanjing City before and after malaria elimination (χ2 =2.400, P > 0.05). Malaria cases mainly acquired Plasmodium infections in African regions, and no significant difference was seen in the proportion of malaria cases returning to Nanjing City from African countries before and after malaria elimination (χ2 = 0.093, P > 0.05). The number of malaria cases peaked in Nanjing City in January and during the period from May to July before elimination, and there was no apparent seasonal variation in the distribution of malaria cases after elimination. The proportion of malaria cases living in Nanjing City was significantly greater after malaria elimination than before elimination (72.15% vs. 55.56%; χ2 = 5.187, P = 0.023). The proportions of businessmen and international students were both 5.05% before malaria elimination, and increased to 15.19% and 13.92% after elimination, respectively (χ2 = 5.229 and 4.229, both P values < 0.05). The percentage of definitive diagnosis of malaria at initial diagnosis was 18.75% in county-level hospitals before malaria elimination and increased to 61.11% after elimination (χ2 = 6.275, P = 0.012), while the proportion of malaria cases with definitive diagnoses in county-level hospitals was 4.04% before malaria elimination and increased to 13.92% after elimination (χ2 = 5.562, P = 0.018). During the period from 2012 to 2020, the proportion of malaria cases with definitive diagnoses within 1 to 3 days post-admission increased from 27.27% in Nanjing City before malaria elimination to 45.57% after elimination (χ2 = 6.433, P = 0.011). Conclusions The epidemic situation of imported malaria remains serious in Nanjing City during the post-elimination stage, and malaria parasite infections predominantly occur in African regions. In addition, there are changes in regional and occupational distributions of malaria cases and the diagnostic capability of malaria increases in county-level hospitals in Nanjing City after malaria elimination. Further improvements in the malaria surveillance system and the diagnostic and treatment capability of malaria in medical institutions at each level are required to consolidate malaria elimination achievements in Nanjing City.

[Comparison of Schistosoma japonicum development between single sexual infection and double sexual infection in mice and rabbits].

OBJECTIVE: To observe the development of Schistosoma japonicum after single sexual infection and double sexual infection respectively. METHODS: A single Oncomelania hupensis snail was infected by a single schistosome miracidium. The larva were induced and released from the snail after 60-day incubation at 26 ℃. The mice were infected by the larva (single sexual infection) and dissected 40 days after the infection. All the worms were collected and the sex of the larvae was determined by the sex of the adult worms. Then, the mice and rabbits were infected by single sex of larvae (single sexual infection) and double sex of larvae (double sexual infection) respectively. The mice and the rabbits were dissected 40 days after the infection. All the worms were collected and measured under a microscope. RESULTS: All the male or female worms were collected from the mice and rabbits after single sexual infection. There were three main forms of worms after dissection of double sexual infection of mice and rabbits: folded mature male and female, male or female. Few folded male and immature female were found. Only the double sexual larva infected mice or rabbits had schistosome eggs in the liver and the liver had typical schistosome egg nodules. The single sexual larva infected mice or rabbits had no schistosome eggs or schistosome egg nodules in the liver tissues. The single male larva could develop to worms with the testis, and with a little smaller size compared to the mature folded male, while the single sexual infection female worm could not develop to the mature stage with much thinner and smaller compared to the mature folded female. CONCLUSIONS: The male or female worms from single sexual infection are smaller than those from double sexual infection (mature worms - folded male and female). So it is necessary to check single sex worms in vessels of intestinal mucosa thoroughly in the sentinel mice when no schistosome eggs were found in the liver.

Clinicopathological features and treatment strategies of intraductal papillary neoplasm of the bile duct / 中华消化外科杂志

Objective:To investigate the clinicopathological features and treatment strategies of intraductal papillary neoplasm of the bile duct (IPNB).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 40 patients with IPNB who were admitted to Peking Union Medical College Hospital from August 2000 to April 2020 were collected. There were 19 males and 21 females,aged (60±14) years. Patients underwent preoperative imaging examination and blood test for evaluation of tumor location, range and resectability. The treatment strategies of patients depended on preoperative examination and their own willingness. Observation indicators: (1) preoperative examinations and tests; (2) treatment; (3) pathological examination; (4) follow-up. Follow-up using outpatient examination, telephone interview and online diagnosis was performed to detect tumor recurrence and survival of patients up to April 2021. Count data were represented as absolute numbers and percentages. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). The Kaplan-Meier method was used to calculate the cumulative survival rate and draw survivla curve. Results:(1) Preoperative examinations and tests: 40 patients received preoperative imaging examination and blood test. Of 40 patients, 33 cases underwent abdominal ultrasonography, 31 cases underwent abdominal computed tomography (CT) examina-tion, 21 cases underwent magnetic resonance imaging (MRI), 15 cases underwent endoscopic retrograde cholangiopancreatography (ERCP), 8 cases underwent position emission tomography CT examination, 6 cases underwent endoscopic ultrasonography; some patients underwent multiple examinations. The main imaging features of IPNB were bile duct dilatation, and intraluminal tumor. Enhanced CT scan showed tumor reinforcement. Preoperative blood tests showed of the 40 patients, 21 cases with abnormal liver function, 17 cases with increased bilirubin, 9 cases with increased carcinoembryonic antigen, and 24 cases with increased CA19-9. (2) Treatment: 35 of 40 patients underwent surgery, 5 patients underwent ERCP and biopsy and didn′t undergo surgery based on their willings. Of 35 patients with surgeries,20 cases underwent hemihepatectomy or lobectomy, 8 cases underwent pancreatico-duodenectomy, 7 cases underwent bile duct tumor resection. The operation time was (262±91)minutes, and volume of intraoperative blood loss was 300 mL(range, 50?2 000 mL). Postopera-tive complications occurred in 6 of 35 patients, including 3 cases with Grade Ⅰ complications and 3 cases with Grade Ⅱ complication according to Clavien-Dindo classi-fication system. (3) Pathological examination: 40 patients were diagnosed as IPNB by pathological examinations. There were 19 and 21 patients with extrahepatic and intrahepatic lesions, respectively. There were 20 benign lesions (15 cases of low or intermediate-grade intraepithelial neoplasia and 5 cases of high-grade intraepithelial neoplasia) and 20 malignant lesions of invasive carcinoma. There were 18 cases with mucus secretion and 22 cases without mucus secretion or information. Five of 35 patients with surgeries had positive margin and the rest of 30 patients had negative margin. A total of 154 lymph nodes were dissected in 21 patients, including 3 positive lymph nodes. (4) Follow-up: 35 of 40 patients were followed up for (53±35)months. Seventeen of 35 patients survived without tumor, and 3 patients survived with tumor of which the time to tumor recurrence were 12, 17, 37 months. Fifteen patients died, with the time interval to death of (30±19)months. The 1-, 3-, and 5-year cumulative survival rates of 35 patients were 88.6%, 73.6%, and 50.7%, respectively.Conclusions:IPNB is rare, with the main imaging features as bile duct dilatation, and intraluminal tumor. The tumor is reinforce-ment after enhanced scan. Surgery is the main treatment for IPNB and lymph node metastasis is rare.

The significance of the flexible loop in the azurin (Az-iso2) from the obligate methylotroph Methylomonas sp. strain J.

The obligate methylotroph Methylomonas sp. strain J produces two azurins (Az-iso1 and Az-iso2) as candidates for electron acceptor from methylamine dehydrogenase (MADH) in the electron-transfer process involving the oxidation of methylamine to formaldehyde and ammonia. The X-ray crystallographic study indicated that Az-iso2 gives two types of crystals (form I and form II) with polyethylene glycol (PEG4000) and ammonium sulfate as the precipitants, respectively. Comparison between the two Az-iso2 structures in forms I and II reveals the remarkable structural changes at the top surface of the molecule around the copper atom. Az-iso2 possesses Gly43 instead of Val43 or Ala43, which is unique among all other azurins around the copper ligand His46, inducing the remarkable structural change in the loop region from Gly37 to Gly43. When the structure of Az-iso2 is superimposed on that of amicyanin in the ternary complex composed of MADH, amicyanin, and cytochrome c(551), the loop of Az-iso2 deeply overlaps with the light subunit of MADH. However, the Az-iso2 molecule is probably able to avoid any steric hindrance with the cognate MADH to form the complex for intermolecular electron-transfer reaction, since the loop containing Gly43 is flexible. We discuss why the electron-transfer activity of Az-iso2 is fivefold higher than that of Az-iso1.

Standardizing Diagnosis of Helicobacter pylori Infection to Improve Diagnostic Accuracy / 胃肠病学

Eradication of Helicobacter pylori (Hp) is important for the prevention and treatment of chronic gastritis, peptic ulcer and gastric cancer. The Chinese consensus on the management of Hp infection has taken "confirmed Hp infection" as an indication for eradication. The World Gastroenterology Organisation global guideline states the "test-and-treat strategy" for Hp infection. Accurate diagnosis of Hp infection is a prerequisite for standardized eradication. There are many methods to diagnose Hp infection. Each has its advantages and disadvantages. Different methods are suitable for different diseases and patients, and each method has strict requirements for reagents, equipment, testers and patients. Therefore, increasing the awareness of physicians and testers about the standardized diagnosis of Hp infection is essential to improve the diagnostic accuracy.

Effect of integrated schistosomiasis control measures on Oncomelania snails in river channels connecting the Yangtze River in Nanjing City / 中国血吸虫病防治杂志

ObjectiveTo evaluate the effectiveness of Oncomelania snails control following the implementation of integrated schistosomiasis control measures in river channels connecting the Yangtze River in endemic areas of Nanjing City. MethodsThe river channels connecting the Yangtze River with snails in Nanjing City were selected as the study pilots. The integrated schistosomiasis control measures implemented in the study pilots were investigated by means of retrospective analyses and field surveys from 1998 to 2019, and the effectiveness of snail control was evaluated. Results Integrated control measures with emphases on environmental improvements including water resource projects for schistosomiasis control were implemented in the study pilots during the period from 1998 to 2019, including river bank concretion with 84.51 km in length, marshland cutting and dredging with 50.41 km in length, building 2 sluices and 3 overflow dams, digging one floodway and snail control with chemical treatment that covered an area of 3 370.80 hm2. No Schistosoma japonicum infection had been detected in snails since the completion of the integrated control measures. In addition, snails had been eliminated in 6 river channels connecting the Yangtze River until 2019, with the snail habitats reducing from 214.33 hm2 to 52.22 hm2 in 10 river channels connecting the Yangtze River and the snail density reducing to below 0.1 snails/0.1 m2 in snail-breeding river channels connecting the Yangtze River. Conclusions The integrated schistosomiasis control measures with emphases on environmental improvements may effectively control snail breeding and spread in rivers connecting the Yangtze River in endemic areas of schistosomiasis; however, the maintenance of the project and snail surveillance and control should be intensified following the completion of the integrated schistosomiasis control measures.