Soil-transmitted helminths, intestinal protozoa and Clonorchis sinensis infections in southeast China.

BACKGROUND: Extensive parasitic diseases epidemiology in Zhejiang province has not been carried out since the second national survey in 2004. Therefore, dynamics in prevalence and infection pattern of the major intestinal parasites should be explored. METHODS: The distribution of three parasites including soil-transmitted helminths (STH), intestinal protozoa and C. sinensis in Zhejiang from 2014 to 2015 were explored. Kato-Katz technique was used for STH and C. sinensis detection, whereas transparent adhesive paper anal swab was used for pinworm detection, and iodine smear was used for protozoa detection. A questionnaire survey on alimentary habits and sanitary behaviors was conducted in half of the studied counties. RESULTS: This study recruited 23,552 participants: 19,935 from rural and 3617 from urban area. Overall prevalence of intestinal helminth infections was 1.80%. In this study, seven helminth species were identified including A. duodenale, N. americanus, Trichuris trichiura, Ascaris lumbricoides, C. sinensis, Fasciolopsis buski and pinworm. The average prevalence of STH infection was 1.71%: 1.94% in rural and 0.44% in urban area. Hookworm was the most prevalent infection at 1.58%: 1.79% in rural and 0.44% in urban area. Prevalence varied considerably in the studied counties. Prevalence was highest in Yongkang county at 10.25%. Only 2.79% of children from rural area were infected with pinworm. A proportion of 0.40% of rural participants were infected with protozoa, whereas Endolimax nana was the most prevalent at 0.23%. C. sinensis showed infection only in one man. Awareness on C. sinensis was 24.47% in rural and 45.96% in urban area, respectively. CONCLUSIONS: Prevalence of STH and protozoa infections declined considerably whereas C. sinensis infections remained few in Zhejiang province compared with the prevalence reported in previous large scale surveys (19.56% for national STH infection in 2004, 18.66% and 4.57% for provincial STH and protozoa infection, respectively in 1999). The findings of this study showed that hookworm, mainly N. americanus remained a parasitic threat to population health, mainly in the central and western Zhejiang. Therefore, more health education regarding fertilization and farming habits is necessary in rural areas. The awareness concerning hookworm infection should be reinforced.

Genetic diversity analysis of PvCSP and its application in tracking of Plasmodium vivax.

BACKGROUND: Plasmodium vivax remains a potential cause of morbidity and mortality for people living where it is endemic. Understanding the regional genetic diversity of P. vivax is valuable for studying population dynamics and tracing the origins of parasites. The Plasmodium vivax circumsporozoite gene (PvCSP) is highly polymorphic and has been used previously as a marker in P. vivax population studies. The aim of this study is to investigate the genetic diversity of the PvCSP, to provide more genetic polymorphism data for further studies on P. vivax population structure, and tracking of the origin of clinical cases. METHODS: Nested PCR and DNA sequencing of the PvCSP were performed to obtain nucleotide sequences of P. vivax isolates collected from Zhejiang province, China, between 2006 and 2014. To investigate the genetic diversity of PvCSP, the nucleotide sequences and amino acid sequences of the PvCSP were analyzed using DNAstar, Mega software and the phylogenetic tree constructed. The relatedness between the polymorphism and infection source were also analyzed using the SPSS software. RESULTS: The 66 P. vivax isolates collected from Zhejiang province were either indigenous cases or cases imported from different regions of the world. All 66 P. vivax isolates belonged to the VK210 variant. Fourteen different Peptide Repeat Motifs (PRMs) were detected in the Central Repeat Region (CRR) of PvCSP, among which, two PRMs of GDRADGQPA and GDRAAGQPA were widely distributed in all isolates. Several polymorphic characteristics of the VK210 variant were observed, including the insertion sequence of 12 peptides, the frequency of the GGNA repeat, the frequency of the PRMs repeat in CRR, and the frequency of the PRM of GNGAGGQAA repeat, which were indicative for tracking the parasite. CONCLUSION: This study presents abundant genetic diversity in the PvCSP marker among P. vivax strains around the world. The genetic data are valuable to expand the polymorphism information on P. vivax, which could be helpful for further study on population dynamics and tracking the origin of P. vivax.

Delta opioid receptor agonist attenuates lipopolysaccharide-induced myocardial injury by regulating autophagy.

BACKGROUND: Previous studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis. METHODS: Male mice were subjected to LPS or vehicle intraperitoneal injection. After LPS injection, mice received either DADLE, Naltrindole or vehicle. ELISA and JC-1 were used to evaluate the level cTnI and Mitochondrial membrane potential. Cardiac ultrastructural and autophagosomes were visualized by transmission electron microscopy. The relative protein levels were analyzed by Western blot. RESULTS: The results showed that treatment with DADLE both immediately or 4 h after LPS intraperitoneal injection could improve the survival rate of mice with endotoxemic. DADLE could ease myocardium ultrastructure injury induced by LPS, this cardioprotective effect was also seen in increased MMP levels, and decreased cTnI levels. Through observation of transmission electron microscopy and Western blot we have discovered that the amount of autophagosome and the expression of autophagy related protein LC3II, Beclin1 were significantly increased with DADLE treatment. DADLE promoted LPS-induced autophagosome maturation as indicated by the increased LAMP-1 protein level and decreased SQSTM1/p62 protein level. The selective δ-opioid receptor antagonist Naltrindole play an opposite effects. CONCLUSIONS: DADLE could improve the survival and protect myocardial dysfunction in mice with LPS-induced endotoxemia. This effect was related to the increase of autophagy.

[Diagnosis and treatment of a local case of Taenia saginata infection in Zhejiang Province].

Objective: To diagnose and provide treatment for a local case of taenia infection in Zhejiang Province and identify the species of the worm. Methods: The information of disease onset, clinical feature and therapeutic process was collected and epidemiological investigation was carried out. The anal cellophane swab was used to detect the eggs. Areca and pumpkin seeds were used for deworming. Morphological observation, PCR amplification and sequencing of cytochrome C oxidase 1(COX1) gene were performed for the discharged worm. Results: The epidemiological results showed that the patient did not go outside Pujiang County in the past two years, and had no history of eating raw pork, beef or animal offal. But she often had barbecues and hot-pot food, occasionally with raw vegetables. Taenia eggs were found on her perianal skin. The discharged worm was suspected to be Taenia saginata or Taenia asiatica by morphological observation. PCR amplification of COX1 resulted in a band of 832 bp, which was 99%, 96% and 88% homologous to COX1 of Taenia saginata (GenBank accession number: AB107239.1), Taenia asiatica (GenBank accession number: AB107235.1) and Taenia solium (GenBank accession number: AB066485.1), respectively. Conclusion: According to the clinical feature, epidemiological information and sequencing results, this case is confirmed to be a local infection of Taenia saginata.

[An Investigation on a Case of Family-clustered Paragonimiasis in Wenzhou City].

Paragonimus infection was reported in a family of 8 members after consuming wine-preserved raw crabs. Seven members developed symptoms of fever, cough, sputum, fatigueness, chest pain, and abdominal pain during 2-3 months after crab feeding, while one member was normal. Serum samples were collected from the 7 members for anti-paragonimus antibody test, with 5 members showing positive, 1 weakly positive and 1 negative. In view of the epidemiological history, clinical symptoms, imaging and laboratory test results, this case was diagnosed to be a family-clustered paragonimus infection.

Evidence for preoperative aspirin improving major outcomes in patients with chronic kidney disease undergoing cardiac surgery: a cohort study.

BACKGROUND: Effects of aspirin on patients with chronic kidney disease (CKD) remains unclear. This study aimed to examine the effect of preoperative aspirin use on postoperative renal function and 30-day mortality in patients with CKD undergoing cardiac surgery. METHODS: A retrospective cohort study was performed on consecutive patients (n = 5175) receiving cardiac surgery in 2 tertiary hospitals. Of all patients, 3585 met the inclusion criteria and underwent the analysis to determine the association of preoperative aspirin with incidence of acute kidney injury (AKI) and death based on estimated glomerular filtration rate (eGFR). RESULTS: Of 3585 patients, 31.5% had CKD (eGFR < 60 mL/min/1.73 m2) at baseline and 27.6% had AKI postoperatively. The baseline eGFR had a nonlinear relationship with the incidence and stages of AKI. As eGFR decreased to 15 to 30 from more than or equal to 90 mL/min/1.73 m2, AKI and 30-day mortality increased to 50.5% from 23.5% and to 11.9% from 2.6%, respectively (P < 0.001). However, preoperative aspirin use was associated with a significant decrease in postoperative AKI and 30-day mortality in patients with CKD undergoing cardiac surgery, in particular, the survival benefit associated with aspirin was greater in patients with CKD (vs normal kidney function): 30-day mortality was reduced by 23.3%, 58.2%, or 70.0% for patients with baseline eGFR more than or equal to 90, 30 to 59, or 15 to 30 mL/min/1.73 m2, respectively (P trend < 0.001). CONCLUSIONS: For patients with CKD undergoing cardiac surgery, preoperative aspirin therapy was associated with renal protection and mortality decline. The magnitude of the survival benefit was greater in patients with CKD than normal kidney function.

[Identification of Trypanosoma Species in Rattus flavipectus and R. losea using Microscopy and PCR Method].

OBJECTIVE: To identify two suspected Trypanosoma species in Rattus found in Zhejiang Province using microscopy and PCR method. METHODS: Blood samples were collected from Rattus losea and R. flavipectus. Blood smears were prepared, and observed under microscope. The morphological indices of trypanosomes were measured and calculated. The genomic DNA was extracted from the trypanosomes, and the specific fragment of Trypanosoma 18S rRNA gene was amplified using PCR. The products were further sequenced and submitted to GenBank. Blast analysis was performed on line in NCBI. RESULTS: Blood samples from Ratts flavipectus and R. losea were collected from Lucheng District and Wencheng County of Wenzhou, respectively. The parasites from R. losea and R. flavipectus were found to possess the characteristic features of Trypanosoma species, such as nucleus, free flagellum, and kinetoplast, etc. The body length was 27.50 µm and 23.80 µm, and the free flagellum length was 9.60 im and 9.20 jim, respectively. The nucleus index was 0.74 and 1.05, the kinetoplast Index was 1.40 and 1.57, respectively. Based on the morphological characteristics and host specificity, the parasites from R. losea and R. flavipectus were identified as Herpetosoma species, mainly found in rodents. The amplified products were about 700 bp by 18S rRNA gene PCR with the DNA isolated from the trypanosomes. The products were further sequenced, and the resulting sequences were submitted to GenBank with assession numbers of KP098535 (from R. losea) and KP098536 (from R. flavipectus). Blast analysis showed that KP098535 was completely homologous with the sequences from Herpetosoma subgenus (AY491765.1, AY491764.1, and AJ223568.1), and KP098536 was completely homologous with Trypanosoma lewisi (AB242273.1, AJ009156.1). CONCLUSION: The Trypanosoma species found from Rattus flavipectus is Trypanosoma lewisi, and the other one belongs to Herpetosoma subgenus, which may be named as Trypanosoma lewisi-like trypanosome.

Development and application of an AllGlo probe-based qPCR assay for detecting knockdown resistance (kdr) mutations in Anopheles sinensis.

BACKGROUND: Anopheles sinensis is one of the most important malaria vectors in China and other Southeast Asian countries. High levels of resistance have been reported in this species due to the long-term use of insecticides, especially pyrethroids, for public health and agricultural purposes. Knockdown resistance (kdr) caused by a single base pair mutation in the gene encoding the sodium channel is strongly associated with pyrethroid insecticide resistance in many Anopheles mosquitoes. There are few methods currently available for detecting kdr mutations in An. sinensis. METHODS: A novel AllGlo probe-based qPCR (AllGlo-qPCR) method was developed to screen for the predominant kdr mutations in An. sinensis mosquitoes from the Jiangsu Province. The results from AllGlo-qPCR, allele-specific PCR (AS-PCR), and TaqMan-MGB probe-based qPCR (TaqMan-qPCR) were compared. A comparative analysis of the equipment required, ease of use and cost of the available methods was also performed. Finally, the AllGlo-qPCR method was used to detect the frequencies of kdr mutations from the other four provinces in central China. RESULTS: Six kdr genotypes were detected in An. sinensis from the Jiangsu Province by DNA sequencing. The AllGlo-qPCR method detected all of the kdr genotypes with a high level of accuracy (97% sensitivity and 98% specificity). AllGlo-qPCR correctly determined the kdr genotypes of 98.73% of 158 An. sinensis samples, whereas TaqMan-qPCR and AS-PCR correctly identified 96.84% and 88.61% of mutations, respectively. Furthermore, the AllGlo-qPCR method is simpler to perform, requires less equipment, and exhibits a moderate expense cost comparing with the other tested methods of kdr mutation detection. Samples collected from four of the other provinces in central China showed a high frequency of kdr mutation in An. sinensis, as detected by the established AllGlo-qPCR method. CONCLUSION: The novel AllGlo-qPCR method developed for kdr mutation detection in An. sinensis exhibits greater specificity and sensitivity than currently available methods and is more cost-effective; therefore, it represents a useful tool for entomological surveillance.

[Iditification of five imported cases of Plasmodium ovale wallikeri infection in Zhejiang Province].

OBJECTIVE: To identify and analyze Plasmodium ovale wallikeri in 5 imported malaria cases, who were detected positive by microscopy and negative by conventional PCR. METHODS: Epidemiological information and blood samples were collected from the five patients. The detection was conducted by microscopy, Rapid Diagnostic Test (RDT) and nested PCR with Plasmodium genus-specific, species-specific and Plasmodium ovale wallikeri-specific primers. The amplified products were sequenced and Blast analysis was performed on line in NCBI. RESULTS: The five patients returned from Africa, and all had a history of malaria. They were microscopically positive for Plasmodium sp., and two cases showed Pan positive RDT result. All blood samples were negative for four Plasmodium spp. by conventional nested PCR, but positive by nested PCR with Plasmodium ovale wallikeri-specific primers. Blast analysis showed that the amplified sequences of the five cases had complete homology with P. ovale wallikeri clone RSH10 18S ribosomal RNA gene (Accession No. KF219561.1). CONCLUSION: The five cases which classified as positive by microscopy while negative by conventional PCR have been confirmed as Plasmodium ovale wallikeri infection by nested PCR with P. ovale wallikeri-specific primers.

[Tracing investigation and diagnosis of one transfusion-transmitted malaria case in Zhejiang Province].

OBJECTIVE: To identify the sources of infection and the mode of transmission of a malaria case with unknown origin. METHODS: Clinical data of the case were collected and the epidemiological investigation was conducted. The blood samples of the patient and the suspected infection source (blood donor) were detected by microscopy, rapid diagnostic test strip (RDT) and nested PCR. RESULTS: The patient did not visited malaria endemic areas. After a blood transfusion, the patient had chills and fever, and was confirmed as falciparum malaria by microscopy with bone marrow and peripheral blood smears and RDT. The blood donor was a worker returned from Africa. Before blood donation she was sick like malaria carrier, and took anti-malarial drug. She was then confirmed as falciparum malaria by RDT and microscopy. The blood samples from the patient and the blood donor were diagnosed as falciparum malaria by nested PCR, and the similarity of the small subunit rRNA (SSU rRNA) sequence was 100%, showing they were mix-infected with K1 and MAD20 genotypes of Plasmodium falciparum. CONCLUSION: This patient is confirmed P. falciparum infection via blood transfusion from a donor who returned from Africa.

Ultrasonography in the intensive care unit: a bibliometrics analysis.

Background: Ultrasonography is widely used in critical care practice. The status of related studies remains unclear. The purpose of this study is to analyze current literature investigating the use of ultrasound in critical care units by using bibliometric analysis. Methods: The Science Citation Index Expanded (SCI-E) database was used for data retrieval. The search formula for literature retrieval was "ultrasound" OR "ultrasonography" AND "intensive care unit" OR "critical care unit" OR "intensive care" OR "critical care". The bibliometric software package of R software was used to analyze the results. Information of related literatures were analyzed. Results: Finally, 3,715 articles were included. The number of published articles and the number of references increased annually. The research fields included medical imaging, critical care medicine, cardiology, etc. The United States has published more documents in this field than other countries and has shown the highest rate of cooperation with other countries. Among the top 10 research institutions with the largest number of publications, 5 are from France and 3 are from the United States. There are many authors from China in the top 10 published studies. Among the top 10 journals with the largest number of published articles, 5 journals are top journals in the field of critical care medicine. Among the top 10 keywords, there are 5 of ultrasound specialty and 2 of critical care medicine. Conclusions: Researches on the use of ultrasound in critical care units are mainly concentrated in several developed countries in Europe and the United States. Chinese research institutions should perform more studies in this field and increase cooperation with institutions from other countries.

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats.

AIM: To investigate the protective effects of hydrogen sulfide (H2S) against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. METHODS: Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35-40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NaHS (28 µmol/kg, ip) was injected before the resuscitation. RESULTS: Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-α, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H2O2 and ·OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin 1 expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NaHS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. CONCLUSION: NaHS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway.

[Species identification in 5 imported cases previously diagnosed as Vivax malaria by parasitological and nested PCR techniques].

OBJECTIVE: To identify the species of malaria parasites in 5 imported cases previously diagnosed as vivax malaria. METHODS: Epidemiological information and blood samples were collected from five patients who returned from Africa and were diagnosed as vivax malaria. The detection was conducted by microscopy, right VIEW rapid malaria test (RDTs) and nested PCR with Plasmodium genus-specific and species-specific primers. The amplified products were sequenced and Blast analysis was performed. RESULTS: Three of the 5 cases had a history of malaria attack. Microscopically, 4 cases were confirmed as Plasmodium ovale infection, 1 (case 1) was co-infected with P. vivax and P. ovale. All 5 cases showed negative RDT results. Nested PCR detection revealed that the 5 cases had a P. ovale-specific fragment (800 bp), while case 1 had a P. vivax-specific fragment (120 bp) concurrently. Blast analysis showed that the amplified sequence of the 5 cases had a high sequence homology (99%) with P. ovale gene for small subunit ribosomal RNA from GenBank, and that of case 1 also shared 99% homology with P. vivax isolate SV5 18S ribosomal RNA gene (GenBank accession number: JQ627157.1). CONCLUSION: Among the five cases, four were infected by Plasmodium ovale, and one was co-infected with both P. vivax and P. ovale.

[Diagnosis and analysis of the first imported ovale malaria case in Wenzhou City].

The first imported case of Plasmodium ovale infection in Wenzhou City was confirmed by microscopy and PCR test. The patient returned from the People's Republic of Congo to Wenzhou for three and a half months presented a history of fever with chills and rigors on April 30, 2012. The results from peripheral blood smear examination and PCR analysis confirmed a diagnosis of P. ovale infection. The patient was treated with chloroquine plus primaquine for eight days and the symptoms improved.

Exosomal ERBB2IP contributes to tumor growth via elevating PSAT1 expression in non-small cell lung carcinoma.

BACKGROUND: Both exosomes and circular RNAs (circRNAs) are involved in tumor growth. Hsa_circ_0001492 (circERBB2IP) has been reported to be overexpressed in plasma exosomes from patients with lung adenocarcinoma, but the biological role of exosomal circERBB2IP in non-small cell lung carcinoma (NSCLC) is indistinct. METHODS: Exosomes isolated from serums and medium samples were validated by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. Relative expression of circERBB2IP was detected by RT-qPCR. Loss-of-function was done to determine the effect of circERBB2IP on NSCLC cell proliferation and migration. Molecular mechanisms associated with circERBB2IP were predicted by bioinformatic analysis and validated by dual-luciferase reporter, RIP, and RNA pulldown assays. In vivo experiments were performed to identify the function of circERBB2IP in NSCLC. RESULTS: We discovered that circERBB2IP expression was correlated with TNM grade, lymph node metastasis and tumor size of NSCLC patients. Upregulation of circERBB2IP was observed in exosomes derived from NSCLC patient's serum and circERBB2IP might be a potential diagnostic biomarker for NSCLC. CircERBB2IP was transmitted between carcinoma cells through exosomes. Knockdown of circERBB2IP lowered cell growth in mouse models and restrained NSCLC cell proliferation and migration. CircERBB2IP could mediate PSAT1 expression via sponging miR-5195-3p. CONCLUSION: In conclusion, circERBB2IP may drive NSCLC growth by the miR-5195-3p/PSAT1 axis in NSCLC, shedding light on a diagnostic biomarker and therapeutic target for NSCLC.

Increasing incidence of Plasmodium ovale and persistent reporting of Plasmodium vivax in imported malaria cases: an analysis of 9-year surveillance data in four areas of China.

Background: This study aimed at exploring the epidemiological pattern of imported malaria in China before malaria elimination in 2021, to provide evidence-based data for preventing malaria re-establishment in China. Methods: Nine-year surveillance data on imported malaria in four provincial-level administrative divisions (PLADs) (Anhui, Chongqing, Guangxi, and Zhejiang) between 2011 and 2019 were thoroughly collected and analyzed. Results: A quite stable trend in imported malaria cases between 2011 and 2019 was observed. In total, 6,064 imported patients were included. Plasmodium falciparum was the most frequently reported species (4,575, 75.6%). Cases of malaria were most frequently imported from Western Africa (54.4%). We identified an increasing trend in P. ovale and a persistence of P. vivax infections among the cases of malaria imported from Western Africa. Most patients (97.5%) were 20-50 years old. Among imported malaria infections, the main purposes for traveling abroad were labor export (4,914/6,064, 81.0%) and business trips (649, 10.7%). Most patients (2,008/6,064, 33.1%) first visited county-level medical institutions when they sought medical help in China. More patients were diagnosed within 3 days after visiting Centers for Disease Control and Prevention (CDCs) or entry-exit quarantine facilities (EQFs) (1,147/1609, 71.3%) than after visiting medical institutions (2,182/3993, 54.6%). Conclusion: Imported malaria still poses a threat to the malaria-free status of China. County-level institutions are the primary targets in China to improve the sensitivity of the surveillance system and prevent the re-establishment of malaria. Health education should focus on exported labors, especially to Western and Central Africa. Increasing trend in P. ovale and persistence of P. vivax infections indicated their underestimations in Western Africa. Efficient diagnostic tools and sensitive monitoring systems are required to identify Plasmodium species in Africa.

Loss of ZBED6 Protects Against Sepsis-Induced Muscle Atrophy by Upregulating DOCK3-Mediated RAC1/PI3K/AKT Signaling Pathway in Pigs.

Sepsis-induced muscle atrophy often increases morbidity and mortality in intensive care unit (ICU) patients, yet neither therapeutic target nor optimal animal model is available for this disease. Here, by modifying the surgical strategy of cecal ligation and puncture (CLP), a novel sepsis pig model is created that for the first time recapitulates the whole course of sepsis in humans. With this model and sepsis patients, increased levels of the transcription factor zinc finger BED-type containing 6 (ZBED6) in skeletal muscle are shown. Protection against sepsis-induced muscle wasting in ZBED6-deficient pigs is further demonstrated. Mechanistically, integrated analysis of RNA-seq and ChIP-seq reveals dedicator of cytokinesis 3 (DOCK3) as the direct target of ZBED6. In septic ZBED6-deficient pigs, DOCK3 expression is increased in skeletal muscle and myocytes, activating the RAC1/PI3K/AKT pathway and protecting against sepsis-induced muscle wasting. Conversely, opposite gene expression patterns and exacerbated muscle wasting are observed in septic ZBED6-overexpressing myotubes. Notably, sepsis patients show increased ZBED6 expression along with reduced DOCK3 and downregulated RAC1/PI3K/AKT pathway. These findings suggest that ZBED6 is a potential therapeutic target for sepsis-induced muscle atrophy, and the established sepsis pig model is a valuable tool for understanding sepsis pathogenesis and developing its therapeutics.

Exogenous hydrogen sulfide protects against traumatic hemorrhagic shock via attenuation of oxidative stress.

OBJECTIVE: This study was designed to investigate the protective effects of exogenous hydrogen sulfide (H(2)S) on trauma-hemorrhagic shock (T-H). MATERIALS AND METHODS: Forty-eight male Sprague-Dawley rats were anesthetized, while 32 were subjected to both midline laparotomy and hemorrhagic shock (35-40 mmHg for 90 min) by bleeding them from the femoral artery. One hour later, resuscitation was initiated with Ringer lactate. NaHS (28 µmol/kg) or vehicle alone was administered intraperitoneally at the onset of resuscitation. Two hours later, eight animals from each group were re-anesthetized to determine cardiac function, blood gas concentrations, and hepatic and renal function. Superoxide dismutase activity (SOD), malondialdehyde concentrations (MDA), and the activity of myeloperoxidase (MPO) in the serum were measured and pulmonary wet/dry (W/D) ratio and histopathologic evaluations performed. RESULTS: NaHS resulted in an increase in mean arterial blood pressure, left ventricular pressure and positive (+dP/dt(max)) and negative (-dP/dt(max)) first derivatives of pressure as compared with the vehicle only group. The pH, PaO(2) and base excess (BE) were increased in the NaHS-treated group compared with the vehicle-treated group. Aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine were reduced in the NaHS-treated group. NaHS also significantly reduced the high mortality rate at 24 h otherwise caused by T-H. The NaHS-treated group showed a remarkable decrease in MDA and MPO concentrations in plasma and an increase in SOD as compared with the vehicle-treated group. Histopathologic analysis indicated less edema, congestion, inflammatory cell infiltration and necrosis in heart, lung, liver and kidney tissue in NaHS-treated group. CONCLUSIONS: The present study demonstrates that exogenous H(2)S administered at an appropriate dose confers protective effects after T-H and resuscitation, by preventing a decrease in the antioxidant defense system.

An exogenous hydrogen sulphide donor, NaHS, inhibits the nuclear factor κB inhibitor kinase/nuclear factor κb inhibitor/nuclear factor-κB signaling pathway and exerts cardioprotective effects in a rat hemorrhagic shock model.

Hemorrhagic shock (HS) is a common condition and leading cause of death in trauma patients universally. Severe inflammatory responses during HS finally lead to multiple-organ failure. Hydrogen sulphide (H2S) is increasingly recognized as an important signaling molecule with various protective effects. In the present study, we investigated the antiinflammatory and cardioprotective effects of an exogenous H2S donor, sodium hydrosulfide (NaHS), in an HS rat model. Male Sprague-Dawley rats were randomly divided into the sham-operated, sham-operated treated with NaHS (28 µmol/kg, intraperitoneally (i.p.)), HS, and HS treated with NaHS (28 µmol/kg, i.p.) groups. The HS groups were subjected to mimicked HS for 1 h and then treated with NaHS or left untreated. The rats were then resuscitated with Ringer lactate solution for 1 h. Myocardial enzymes and inflammatory cytokines were evaluated. Morphologic changes in cardiac tissue and ultrastructural injury were also analyzed. HS resulted in significant hemodynamic deterioration and increased myocardial enzyme and inflammatory cytokine levels. Intraperitoneal administration of NaHS significantly prevented hemodynamic deterioration and decreased the elevation of myocardial enzymes. NaHS also inhibited the nuclear factor κB inhibitor kinase (IKK)/nuclear factor κB inhibitor (IκB)/nuclear factor κB (NF-κB) signaling pathway. The results suggest that NaHS exerts cardioprotective effects against HS. The protective effects of NaHS may occur via down-regulation of the IKK/IκB/NF-κB signaling pathway.

[Pathogen identification and clinical diagnosis for one case infected with Babesia].

OBJECTIVE: To identify the pathogen and make diagnosis on a case who was misdiagnosed as malaria. METHODS: Clinical and epidemiological information of the suspected case was collected. Blood samples during hospitalization were collected and examined microscopically. Genomic DNA from the blood samples was amplified by Babesia 18S RNA genus- and species- specific primers, respectively, and the amplified products were used in sequencing and BLAST sequence analysis. RESULTS: The case had a fever over 20 days repeatedly with anaemia (RBC 2.59 x 10(12), HB 5.5 g/L) and hepatosplenomegaly. The unidentified parasites were found in the bone marrow and blood smear after Giemsa staining. Epidemiological information revealed that this case had a history of blood transfusion and tick bites. 1 625 bp and 449 bp band generated by PCR amplification from blood sample using Babesia genus- and species-specific primers, and the sequence homology was 99% in comparison to Babesia microti (AB241632) with BLAST analysis. CONCLUSION: The clinical information, epidemiological history, and the PCR identification confirm the diagnosis of Babesia microti infection.