c‐Jun N‐terminal kinase is largely involved in the regulation of tricellular tight junctions via tricellulin in human pancreatic duct epithelial cells

Tricellulin (TRIC) is a tight junction protein at tricellular contacts where three epithelial cells meet, and it is required for the maintenance of the epithelial barrier. To investigate whether TRIC is regulated via a c‐Jun N‐terminal kinase (JNK) pathway, human pancreatic HPAC cells, highly expressed at tricellular contacts, were exposed to various stimuli such as the JNK activators anisomycin and 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), and the proinflammatory cytokines IL‐1β, TNFα, and IL‐1α. TRIC expression and the barrier function were moderated by treatment with the JNK activator anisomycin, and suppressed not only by inhibitors of JNK and PKC but also by siRNAs of TRIC. TRIC expression was induced by treatment with the PKC activator TPA and proinflammatory cytokines IL‐1β, TNFα, and IL‐1α, whereas the changes were inhibited by a JNK inhibitor. Furthermore, in normal human pancreatic duct epithelial cells using hTERT‐transfected primary cultured cells, the responses of TRIC expression to the various stimuli were similar to those in HPAC cells. TRIC expression in tricellular tight junctions is strongly regulated together with the barrier function via the JNK transduction pathway. These findings suggest that JNK may be involved in the regulation of tricellular tight junctions including TRIC expression and the barrier function during normal remodeling of epithelial cells, and prevent disruption of the epithelial barrier in inflammation and other disorders in pancreatic duct epithelial cells. J. Cell. Physiol. 225: 720–733, 2010. © 2010 Wiley‐Liss, Inc.     

Trichoderma harzianum antagonistic activity and competition for seed colonization against seedborne pathogenic fungi of sunflower

This study investigated the antagonistic effects of Trichoderma harzianum isolate (TRIC8) on mycelial growth, hyphal alteration, conidial germination, germ tube length and seed colonization by the seedborne fungal pathogens Alternaria alternata, Bipolaris cynodontis, Fusarium culmorum and F. oxysporum, the causes of seedling rot in over 30% of sunflowers. The antagonistic effect of TRIC8 on mycelial growth of pathogens was evaluated on dual culture that included two inoculation assays: inoculation of antagonist at 48 h before pathogen (deferred inoculation) and inoculation at the same time with pathogen (simultaneous inoculation). TRIC8 inhibited mycelial growth of the fungal pathogens between 70·67 and 76·87% with the strongest inhibition seen with deferred inoculation. Alterations in hyphae were observed in all pathogens. Conidial germination of F. culmorum was inhibited by most of the fungal pathogens (38·28%) by TRIC8. Inhibition of germ tube length by the antagonist varied from 31·83 to 37·67%. In seed colonization experiments, TRIC8 was applied in combination with each pathogen to seeds of a sunflower genotype that is highly tolerant to downy mildew. Seed death was inhibited by TRIC8 and the antagonist did not allow growth of A. alternata, B. cynodontis and F. culmorum on seeds and inhibited the growth of F. oxysporum at the rate of 58·32%.     

重症监护室烧伤感染患者脓毒症的病原菌分布及影响因素研究

目的:探讨重症监护室(ICU)烧伤感染患者脓毒症的发生情况及病原菌分布,并分析其危险因素,为防治ICU烧伤感染患者脓毒症提供理论依据。方法:收集我院2016年7月-2019年7月期间的86例ICU烧伤感染患者的临床资料,依据是否发生脓毒症,将其分为脓毒症组和非脓毒症组,比较两组的基本资料等情况,分析ICU烧伤感染患者脓毒症的发生率及病原菌分布,并分析ICU烧伤感染患者脓毒症发生的影响因素。结果:86例ICU烧伤感染患者中有33例发生脓毒症,发生率为38.37%;ICU烧伤感染患者脓毒症病原菌主要是革兰阴性杆菌(占54.55%),其次是革兰阳性球菌(占42.42%);单因素结果分析发现,烧伤至入院时间、合并糖尿病、吸入性损伤、首次手术时间以及烧伤面积与ICU烧伤感染患者脓毒症的发生有关(P<0.05);多因素Logistic回归分析发现,首次手术时间>2d、TBSA>50%是ICU烧伤感染患者脓毒症发生的独立危险因素(P<0.05)。结论:ICU烧伤感染患者易发生脓毒症,首次手术时间>2d以及TBSA>50%是其发生的独立危险因素,临床应采取针对性预防措施,以降低ICU烧伤感染患者脓毒症发生率。     

乳酸和APACHEⅡ评分在评估老年脓毒症患者预后中的应用

目的：研究乳酸和急性生理学及慢性健康状况评分（APACHE Ⅱ评分）对老年脓毒症患者预后的评估作用。方法：老年脓毒症患者96例,按照入院时血乳酸值分成升高者60例,乳酸正常者36例,比较两组的病死率、休克、机械通气和MODS发生率、APACHE Ⅱ评分的区别;根据APACHE Ⅱ评分（〈15、15～24、≥25）分为3组,比较每组患者的病情和预后区别。结果：乳酸升高组老年脓毒症患者的机械通气、休克发生率、MODS发生率、APACHE Ⅱ评分明显大于乳酸正常组（P〈0.05）,病死率明显上升（28.3%vs 2.7%）,（P=0.005）;随着APACHE Ⅱ评分增高,患者病情逐渐加重,休克发生率和住院病死率明显升高,（P〈0.05）,患者乳酸水平也明显增高（P〈0.05）。结论：血乳酸和APACHE Ⅱ评分都可以评估老年脓毒症患者病情严重和预后,两者升高提示预后差。     

Bioinformatic Characterization of the Trimeric Intracellular Cation-Specific Channel Protein Family

Trimeric intracellular cation-specific (TRIC) channels are integral to muscle excitation–contraction coupling. TRIC channels provide counter-ionic flux when calcium is rapidly transported from intracellular stores to the cell cytoplasm. Until recently, knowledge of the presence of these proteins was limited to animals. We analyzed the TRIC family and identified a profusion of prokaryotic family members with topologies and motifs similar to those of their eukaryotic counterparts. Prokaryotic members far outnumber eukaryotic members, and although none has been functionally characterized, the evidence suggests that they function as secondary carriers. The presence of fused N- or C-terminal domains of known biochemical functions as well as genomic context analyses provide clues about the functions of these prokaryotic homologs. They are proposed to function in metabolite (e.g., amino acid/nucleotide) efflux. Phylogenetic analysis revealed that TRIC channel homologs diverged relatively early during evolutionary history and that horizontal gene transfer was frequent in prokaryotes but not in eukaryotes. Topological analyses of TRIC channels revealed that these proteins possess seven putative transmembrane segments (TMSs), which arose by intragenic duplication of a three-TMS polypeptide-encoding genetic element followed by addition of a seventh TMS at the C terminus to give the precursor of all current TRIC family homologs. We propose that this family arose in prokaryotes.     

Clinical Value of Teichoic Acid Antibody Titers in the Diagnosis and Management of the Staphylococcemias

Differentiation of endocarditic from nonendocarditic Staphylococcus aureus (SA) septicemia is prognostically and therapeutically important. A study of 68 cases of either SA or streptococcal sepsis, including 50 cases of SA sepsis of both cardiac and noncardiac origin, was done to determine the presence and titer of serum teichoic acid antibodies (TAA''s) by double immunodiffusion. Thirty-seven uninfected controls were also examined. There was no statistical difference in either incidence or peak TAA titers in endocardial versus deepseated, extracardiac SA sepsis. However, in both of these groups, incidence and peak titers were significantly higher than in intravascular catheter-related SA sepsis, streptococcal endocarditis and controls (P<0.05). Peak TAA titers in SA sepsis develop on admission or shortly thereafter (6 to 11 days) and permit early decisions on degree of tissue infection, likelihood of metastatic seeding and necessity for higher-dose, longer-term antibiotic therapy.Cases of catheter-related SA sepsis with no clinical evidence of metastatic SA seeding and with negative or low-titered (1:1) TAA''s were classified as superficial sepsis. Treatment consisted of short-term, low-dose antistaphylococcal regimens and catheter removal. In posttherapy follow-up after 6 to 12 weeks, all of the patients were cured and no signs of endocarditis or deepseated SA infection developed.     

Outer Membrane Vesicles Derived from Escherichia coli Induce Systemic Inflammatory Response Syndrome

Sepsis, characterized by a systemic inflammatory state that is usually related to Gram-negative bacterial infection, is a leading cause of death worldwide. Although the annual incidence of sepsis is still rising, the exact cause of Gram-negative bacteria-associated sepsis is not clear. Outer membrane vesicles (OMVs), constitutively secreted from Gram-negative bacteria, are nano-sized spherical bilayered proteolipids. Using a mouse model, we showed that intraperitoneal injection of OMVs derived from intestinal Escherichia coli induced lethality. Furthermore, OMVs induced host responses which resemble a clinically relevant condition like sepsis that was characterized by piloerection, eye exudates, hypothermia, tachypnea, leukopenia, disseminated intravascular coagulation, dysfunction of the lungs, hypotension, and systemic induction of tumor necrosis factor-α and interleukin-6. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of sepsis, suggesting OMVs as a new therapeutic target to prevent and/or treat severe sepsis caused by Gram-negative bacterial infection.     

脓毒症诊断的生物学标志物的研究进展

脓毒症是由致病微生物感染引发的全身炎症反应综合征(SIRS),合并血压降低且经快速液体复苏后血压仍不能恢复正常者称为脓毒性休克(Septic shock),其中一部分患者发展为多器官功能障碍综合症(MODS)。由于目前临床上仍缺乏早期敏感性诊断手段,脓毒症病死率居高不下。每10万人口中约50-300人会发生严重脓毒症,其短期死亡率达20%-25%,当发展为脓毒性休克时其死亡率达50%。随着分子生物学和现代生物技术的不断发展,人们发现多种生物标志物在脓毒症的早期诊断、病情及预后判断,疗效评估中发挥重要作用。因此深入了解脓毒症病理生理机制中不同生物标志物的意义及价值,对于脓毒症及其并发症的早期识别及干预,降低患者病死率及改善患者生活质量有积极意义。本文综述了近几年来对脓毒症的诊断和预后有一定价值的主要标志物及其应用。     

Prophylactic co-trimoxazole in biliary surgery.

A double-blind study was conducted to test the prophylactic effect of a single dose of co-trimoxazole on the incidence of septic complications after elective cholecystectomy. Forty-eight patients received co-trimoxazole and 47 placebo. Wound sepsis occurred in 10 (21%) of the controls but in only 2 (4%) of the treated group, and the incidences of pulmonary complications were 49% (23 cases) and 19% (9) respectively. These differences were significnat. Wound sepsis after cholecystectomy occurs mostly in patients with infected bile. Co-trimoxazole given by intravenous infusion rapidly achieves a high concentration in the palsma and is effective against most biliary pathogens.     

The Effect of Hospital Volume on Mortality in Patients Admitted with Severe Sepsis

Importance

The association between hospital volume and inpatient mortality for severe sepsis is unclear.

Objective

To assess the effect of severe sepsis case volume and inpatient mortality.

Design Setting and Participants

Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011.

Exposures

The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles.

Main Outcomes and Measures

Inpatient mortality.

Results

Compared with the highest tertile of severe sepsis volume (>60 cases per year), the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year) was 1.188 (95% CI: 1.074–1.315), while the odds ratio was 1.090 (95% CI: 1.031–1.152) for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64–38.03) for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51–32.64) for hospitals with the highest volume.

Conclusions and Relevance

We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients.     

新生儿坏死性小肠结肠炎病原菌分布、耐药性及发病的影响因素分析

摘要 目的：观察新生儿坏死性小肠结肠炎（NEC）病原菌分布、耐药性,并分析NEC患儿发病的影响因素。方法：选取2016年8月~2020年9月期间在我院接受治疗的NEC患儿50例（NEC组）,另选取同期于我院出生的100例健康新生儿作为对照组。观察NEC患儿病原菌分布、耐药性,并分析NEC发病的影响因素。结果：50例NEC患儿共培养出病原菌63株。病原菌中革兰阴性菌38株,占比60.32%;革兰阳性菌23株,占比36.51%;真菌2株,占比3.17%。大肠埃希菌、肺炎克雷伯菌均对氧氟沙星、头孢哌酮、头孢他啶、头孢唑林、阿莫西林、氨苄青霉素、环丙沙星、头孢曲松的敏感性较低,对亚胺培南/西司他丁、哌拉西林/他唑巴坦、美罗培南、多粘菌素高度敏感。单因素分析结果显示,NEC发病与新生儿体重、母乳喂养、产前使用糖皮质激素、妊娠期糖尿病、妊娠期高血压、新生儿Apgar评分、是否合并肺部感染、合并败血症有关（P<0.05）。多因素Logistic回归分析发现：母乳喂养是NEC发病的保护因素,合并败血症、妊娠期糖尿病、新生儿体重、合并肺部感染、新生儿Apgar评分均是NEC发病的危险因素（P＜0.05）。结论：NEC患儿的病原菌以革兰阴性菌为主,同时影响NEC发病的因素较多,应结合相关的影响因素制定针对性干预或治疗措施,以减少NEC的发病风险。     

Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee replacement: a randomised study.

In a multicentre study of sepsis after total hip or knee replacement the operations performed by each surgeon were allocated at random between control and ultraclean-air operating rooms. Records were obtained from over 8000 such operations. In the patients whose prostheses were inserted in an operating room ventilated by an ultraclean-air system the incidence of joint sepsis confirmed at reoperation within the next one to four years was about half that of patients who had had the operation in a conventionally ventilated room at the same hospital. When whole-body exhaust-ventilated suits had been worn by the operating team in a theatre ventilated by an ultraclean-air system the incidence of sepsis was about a quarter of that found after operations performed with conventional ventilation. When all groups in the trial were considered together the analysis showed deep sepsis after 63 out of 4133 operations in the control group (1.5%) and after 23 out of 3922 operations in the ultraclean-air groups (0.6%) (ratio 2.6, 95% confidence limits 1.6-4.2; p less than 0.001). The design of the study did not include a strictly controlled test of the effect of prophylactic antibiotics, but their use was associated with a lower incidence of sepsis than in patients who had received no antibiotic prophylaxis at their operations (0.6% (34/5831) v 2.3% (52/2221); ratio 4.0).     

谷氨酰胺对脓毒症患者肠粘膜屏障功能和免疫功能的影响

目的:研究谷氨酰胺对脓毒症患者肠道黏膜屏障功能和免疫功能的影响。方法:将2012年10月至2013年10本院收治的40例脓毒症患者随机分为治疗组和对照组,每组20例。两组患者均给予常规对症治疗,治疗组在此基础上加用谷氨酰胺治疗,对照组接受安慰剂治疗。采用分光光度法监测其血清D-乳酸水平,高效液相色谱法监测尿乳果糖/甘露醇(L/M)值。对比两组肠道黏膜屏障功能和免疫功能指标及ARDS、MODS发生率。结果:治疗后,治疗组ARDS和MODS发生率分别为24.1%,17.2%,均低于对照组的38.9%,33.3%,两组比较差异均有统计学意义(P0.05);治疗14 d后,治疗组D-乳酸及尿L/M水平较对照组明显降低,血清Ig G、Ig M、CD4+和CD4+/CD8+水平均增高,两组比较差异均有统计学意义(P0.05)。结论:谷氨酰胺治疗脓毒性患能明显改善肠道黏膜屏障功能,促进患者免疫功能和营养状态的提高,同时还能够降低患者肠道细菌、内毒素移位。     

不同角膜表面处理方式在全飞秒SMILE手术中的应用效果分析

摘要 目的：探讨不同角膜表面处理方式在全飞秒SMILE手术中的应用效果。方法：选择2021年10月至2022年9月来我院择期行全飞秒SMILE手术的患者50例,根据先右后左手术原则,观察眼与对照眼没有固定左右眼,观察眼25例选择右眼,25例选择左眼,对照眼反之选择另一眼,观察眼使用开睑器开睑后用三角海绵擦拭清洁角膜表。对照眼眼自净（眨眼）后使用开睑器开眼睑。对比观察眼与对照眼的角膜光密度、角膜表面颗粒物质计数、角膜表面湿度、术中负压吸引完成时间、失吸比例、OBL发生率,分析50例患者的舒适度。结果：观察眼的角膜光密度为16.33±2.12,对照组为16.85±2.58,组间对比无统计学意义（t=-1.101,P=0.274）。对照眼的表面颗粒物质计数明显较观察眼低,角膜表面湿度明显较观察眼高（P<0.05）。对照眼与观察组术中负压吸引完成时间、失吸比例对比无统计学意义（P>0.05）。观察眼中OBL发生率为6.00 %,对照眼中OBL发生率为2.00 %,组间对比无统计学意义（P=0.617>0.05）。50例患者中对三角海绵擦拭角膜感觉恐惧者占比32.00%（16/50）,三角海绵擦拭角膜后对注视绿点存在影响者占比20.00 %（10/50）,手术中选择三角海绵擦拭角膜者20例,占比40.00 %（20/50）,选择眼自净（眨眼）者30例,占比60.00 %（30/50）。结论：眼自净（眨眼）可以代替三角海绵擦拭角膜,用于全飞秒SMILE手术,提高患者舒适度。     

Two cases of human thelaziasis and brief review of Korean cases

The present study was performed to describe 2 cases of human thelaziasis (HT) which occurred in Gyeongsangnam- do and to briefly review the previously reported Korean cases. A 58-year old woman, residing in Hadong-gun, Gyeongsangnam-do, came to Gyeongsang National University Hospital (GNUH) complaining of foreign body sensation and itching of the right eye in March 2000. Total 6 adult nematodes of Thelazia callipaeda (2 males and 4 females) were detected in her right eye. A 80-year old man, residing in Jinju-si, Gyeongsangnam-do, came to GNUH complaining of foreign body sensation, itching, and pain of the right eye in December 2007. A total of 5 worms (4 females and 1 degenerated) were removed from his right eye. We analyzed characteristics of the total 39 Korean HT cases reported to date, including the present 2 cases. Most of the cases (71.8%) occurred in Seoul and Gyeonggi-do before 2000, and 21 cases (53.8%) were males and 18 (46.2%) were females. The prevalence was higher in younger ages below 30 years (48.7%) than 31-60 years (41.0%) and over 61 years (10.3%). The seasonal prevalence showed a higher incidence in autumn (43.6%) than in other seasons. Most of the cases (94.9%) were conjunctival sac infections and only 2 (5.1%) were intraocular cases. The present 2 HT cases are the first reported cases in Gyeongsangnam-do. Some characteristics of Korean HT cases were analyzed.     

The Impact of Nationwide Education Program on Clinical Practice in Sepsis Care and Mortality of Severe Sepsis: A Population-Based Study in Taiwan

Objectives

We investigated the effect of a nationwide educational program following surviving sepsis campaign (SSC) guidelines. Physicians’ clinical practice in sepsis care and patient mortality rate for severe sepsis were analyzed using a nationally representative cohort.

Methods

Hospitalizations for severe sepsis with organ failure from 1997 to 2008 were extracted from Taiwan’s National Health Insurance Research Database (NHIRD), and trends in sepsis incidence and mortality rates were analyzed. A before-and-after study design was used to evaluate changes in the utilization rates of SSC items and changes in severe sepsis mortality rates occurred after a national education program conducted by the Joint Taiwan Critical Care Medicine Committee since 2004. A total of 39,706 hospitalizations were analyzed, which consisted of a pre-intervention cohort of 14,848 individuals (2000-2003) and a post-intervention cohort of 24,858 individuals (2005-2008).

Results

The incidence rate of severe sepsis increased from 1.88 per 1,000 individuals in 1997 to 5.07 per 1,000 individuals in 2008. The cumulative mortality rate decreased slightly from 48.2% for the pre-intervention cohort to 45.9% for the post-intervention cohort. The utilization rates of almost all SSC items changed significantly between the pre-intervention and post-intervention cohorts. These changes of utilization rates were found to be associated with mild reduction in mortality rate.

Conclusion

The nationwide education program through a national professional society has a significant impact on physicians’ clinical practice and resulted in a slight but significant reduction of severe sepsis mortality rate.     

Tricellulin is a tight-junction protein necessary for hearing

The inner ear has fluid-filled compartments of different ionic compositions, including the endolymphatic and perilymphatic spaces of the organ of Corti; the separation from one another by epithelial barriers is required for normal hearing. TRIC encodes tricellulin, a recently discovered tight-junction (TJ) protein that contributes to the structure and function of tricellular contacts of neighboring cells in many epithelial tissues. We show that, in humans, four different recessive mutations of TRIC cause nonsyndromic deafness (DFNB49), a surprisingly limited phenotype, given the widespread tissue distribution of tricellulin in epithelial cells. In the inner ear, tricellulin is concentrated at the tricellular TJs in cochlear and vestibular epithelia, including the structurally complex and extensive junctions between supporting and hair cells. We also demonstrate that there are multiple alternatively spliced isoforms of TRIC in various tissues and that mutations of TRIC associated with hearing loss remove all or most of a conserved region in the cytosolic domain that binds to the cytosolic scaffolding protein ZO-1. A wild-type isoform of tricellulin, which lacks this conserved region, is unaffected by the mutant alleles and is hypothesized to be sufficient for structural and functional integrity of epithelial barriers outside the inner ear.     

The Continuum of Maternal Sepsis Severity: Incidence and Risk Factors in a Population-Based Cohort Study

Objective

To investigate the incidence and risk factors associated with uncomplicated maternal sepsis and progression to severe sepsis in a large population-based birth cohort.

Methods

This retrospective cohort study used linked hospital discharge and vital statistics records data for 1,622,474 live births in California during 2005–2007. Demographic and clinical factors were adjusted using multivariable logistic regression with robust standard errors.

Results

1598 mothers developed sepsis; incidence of all sepsis was 10 per 10,000 live births (95% CI = 9.4–10.3). Women had significantly increased adjusted odds (aOR) of developing sepsis if they were older (25–34 years: aOR = 1.29; ≥35 years: aOR = 1.41), had ≤high-school education (aOR = 1.63), public/no-insurance (aOR = 1.22) or a cesarean section (primary: aOR = 1.99; repeat: aOR = 1.25). 791 women progressed to severe sepsis; incidence of severe sepsis was 4.9 per 10,000 live births (95% CI = 4.5–5.2). Women had significantly increased adjusted odds of progressing to severe sepsis if they were Black (aOR = 2.09), Asian (aOR = 1.59), Hispanic (aOR = 1.42), had public/no-insurance (aOR = 1.52), delivered in hospitals with <1,000 births/year (aOR = 1.93), were primiparous (aOR = 2.03), had a multiple birth (aOR = 3.5), diabetes (aOR = 1.47), or chronic hypertension (aOR = 8.51). Preeclampsia and postpartum hemorrhage were also significantly associated with progression to severe sepsis (aOR = 3.72; aOR = 4.18). For every cumulative factor, risk of uncomplicated sepsis increased by 25% (95% CI = 17.4–32.3) and risk of progression to severe sepsis/septic shock increased by 57% (95% CI = 40.8–74.4).

Conclusions

The rate of severe sepsis was approximately twice the 1991–2003 national estimate. Risk factors identified are relevant to obstetric practice given their cumulative risk effect and the apparent increase in severe sepsis incidence.     

Eye injuries in squash: a preventable disease.

As more Canadians are taking up squash the incidence of eye injuries is increasing dramatically. Over 2-1/2 years, 23 cases from one urban practice were examined. Almost half of the group required inhospital treatment. Five patients sustained a permanent decrease in vision; these cases involved three corneal scars, one cataract and one macular cyst. Patients wearing glasses or hard contact lenses appear to be more susceptible to serious eye injury. Experience does not appear to reduce the likelihood of eye injuries; the patients in this study had played squash for 5.6 years on the average. Consequently the medical profession must take the lead by encouraging squash players to use protective equipment now available to reduce the incidence of these injuries that pose so much personal hazard.