Limited Propagation of SARS-CoV-2 among Children in a Childcare Center, Canada, 2021.

An outbreak of severe acute respiratory syndrome coronavirus 2 with no definitive source and potential exposure to variants of concern was declared at a childcare center in Ontario, Canada, in March 2021. We developed a robust outbreak management approach to detect, contain, and interrupt this outbreak and limit propagation among children.

Isolation, identification and virulence gene characterization of Aeromonas dhakensis isolated from sea lion (Zalophus californianus).

Species of Aeromonas are ubiquitous pathogens of fish and aquatic animals and can infect humans and other animals through the food chain. However, there are few reports of marine mammalian infections. In 2020, a sea lion (Zalophus californianus) died acutely at an aquarium in Harbin, Heilongjiang Province, China. In order to explore the cause of death, we dissected the animal and observed pathological changes. Ogans were aseptically collected and used for bacterial isolation and culture. This revealed that the sea lion had died of sepsis caused by a bacterial infection. Isolated bacteria were investigated by morphology, biochemical phenotype and molecular identification, and this determined the pathogen as A. dhakensis. The isolate contained six virulence genes, hlyA, aerA, act, lafA, ela, fla, and was susceptible to most antibiotics. This is the first report of A. dhakensis associated with septicaemia in pinnipeds and a description of its virulence and resistance profiles. Its presence in aquatic environments poses a potential threat to marine mammals.

COVID-19 Vaccine Uptake in Southeastern Ontario, Canada: Monitoring and Addressing Health Inequities.

CONTEXT: Implementation of a population-based COVID-19 vaccine strategy, with a tailored approach to reduce inequities in 2-dose coverage, by a mid-sized local public health agency in southeastern Ontario, Canada. PROGRAM: Coverage maps and crude and age-standardized coverage rates by material and social deprivation, urban/rural status, and sex were calculated biweekly and reviewed by local public health planners. In collaboration with community partners, the results guided targeted strategies to enhance uptake for marginalized populations. EVALUATION: The largest gaps in vaccine coverage were for those living in more materially deprived areas and rural residents-coverage was lower by 10.9% (95% confidence interval: -11.8 to -10.0) and 9.3% (95% confidence interval: -10.4 to -8.1) for these groups compared with living in less deprived areas and urban residents, respectively. The gaps for all health equity indicators decreased statistically significantly over time. Targeted strategies included expanding clinic operating hours and availability of walk-in appointments, mobile clinics targeted to marginalized populations, leveraging primary care partners to provide pop-up clinics in rural and materially and socially deprived areas, and collaborating with multiple partners to coordinate communication efforts, especially in rural areas. DISCUSSION: The scale and scope of monitoring and improving local vaccine uptake are unprecedented. Regular review of health equity indicators provided critical situational awareness for decision makers, allowing partners to align and tailor strategies locally and in collaboration with one another. Health care providers and pharmacies/pharmacists are key partners who require innovative support to increase uptake in marginalized groups. Continued engagement of other community partners such as schools, municipalities, and local service groups is also crucial. A "hyper local" approach is needed along with commitment from partners in all sectors and at all levels to reduce barriers to vaccination that lie further upstream for marginalized groups.

[The risk factors of first recurrence in ischemic stroke patients in different periods after first attack].

Objective: To investigate the risk factors of first recurrence in ischemic stroke patients at different periods after first attack. Methods: The subjects were from the screening population of China National Stroke Screening Survey (CNSSS) from 2013 to 2015. The basic demographic information, stroke history, influencing factors and modified Rankin Scale (mRs) scores were collected by using standardized face-to-face questionnaires. A case-control study was conducted to investigate the risk factors of first recurrence in ischemic stroke patients who relapsed for the first time within 12 months, 24 months and 36 months as the case group and non-recurrent ischemic stroke patients as the control group. Further, the subjects were stratified into different subgroups by age, gender and urban-rural distribution to investigate the risk factors of first recurrence in different periods. Results: Diabetes (OR=1.71, 95%CI: 1.08-2.71) and coronary heart disease (OR=1.55, 95%CI: 1.09-2.19) were significantly associated with the risk of first recurrence within 12 months after the first onset of ischemic stroke. The diabetes was significantly associated with the risk of first recurrence within 24 months (OR=1.94, 95%CI: 1.33-2.83) and 36 months (OR=1.64, 95%CI: 1.15-2.34) after the first onset of ischemic stroke. With the increase of mRs score, the risk of first recurrence within 12 months, 24 months and 36 months in ischemic stroke patients increased significantly. In the same period, the risk factors of ischemic stroke recurrence differed in patients with different age, gender and urban-rural distribution. Conclusions: The risk factors of first recurrence in ischemic stroke patients are diverse at different periods after the first onset of ischemic stroke. In different subgroups, the risk factors of first recurrence and the strength of its corresponding association are also different.

[The epidemiological characteristics and adherence to hypoglycemic agents of ischemic stroke patients with diabetes].

Objective: To investigate the epidemiological characteristics and adherence to hypoglycemic agents of the ischemic stroke patients combined with diabetes. Methods: The study recruited 23 044 ischemic stroke cases from 2013-2015 screening period of China National Stroke Screening Survey. Standardized questionnaires were used to obtain information on demographic data, stroke history, the presence of influence factors, as well as the type of stroke, diagnosis date, frequency, chronic diseases history and hypoglycemic therapy. We used logistics model to investigate the possible risk factors of ischemic stroke combined with diabetes, and calculated the population attributable risk proportion (PARP). We also investigate the adherence to hypoglycemic agents. Results: The mean age of 23 044 ischemic stroke patients was (64.99±9.42) years old, 50.91% were males (11 731). In ischemic stroke patients, 21.52% had diabetes. According to the results of logistics model, ischemic stroke patients with hypertension, dyslipidemia, atrial fibrillation or family history of stroke had higher risk to combine with diabetes, their Odds Ratios (OR) were 2.18 (1.87-2.55), 1.99 (1.78-2.23), 1.64 (1.39-1.92) and 1.19 (1.06-1.33). Considering the prevalence of each influence factor in ischemic stroke patients, atrial fibrillation had the highest PARP (95%CI) of 62.65% (61.27%-63.76%). In ischemic stroke patients combined with diabetes, 70.73% (3 463/4 896) had taken hypoglycemic agents. Conclusion: There still were a large number of ischemic stroke patients combined with diabetes and a low rate of adherence to hypoglycemic agents.

[The association of health-related behavior and the risk of stroke in people with hypertension].

Objective: To investigate the association between the combination of different health-related behaviors and the risk of stroke in people with hypertension. Methods: The data in this study were obtained from the China National Stroke Screening Survey (CNSSS). The case group was the people with hypertension who were also diagnosed as the first-ever stroke cases (total stroke and ischemic stroke) during 2013-2014 screening period. Their corresponding controls (1∶3 frequency-matched for age group and urban/rural ratio) were randomly selected from individuals with hypertension without stroke. The information on demographic data, stroke history, influence factors and health-related behaviors (non-smoking, normal body mass index maintenance and physical activity) was obtained using standardized face-to-face questionnaires. Univariate analysis included t-test and Chi-square test. Multivariate analysis included unconditional logistic regression. Results: There were 603 total stroke cases (1 909 controls) and 536 ischemic stroke cases (1 608 controls) in men with hypertension, and 600 total stroke cases (1 800 controls) and 534 ischemic stroke cases (1 602 controls) in women with hypertension. We found that women with three health-related behaviors had lower risk of total stroke (OR=0.29, 95%CI: 0.11-0.79) and ischemic stroke (OR=0.28, 95%CI: 0.10-0.77). Only the combination of non-smoking and physical activity was significantly associated with the decreased risk of total stroke (OR=0.30, 95%CI: 0.11-0.78) and ischemic stroke (OR=0.32, 95%CI: 0.12-0.87). We had not found significant association between the combination of different health-related behaviors and risk of total stroke and ischemic stroke (P>0.05) in men. Conclusion: This study indicated that health-related behavior intervention might be more effectively to prevent stroke in women with hypertension, especially the smoking control and physical activity.

[Gender-specific factors of ischemic stroke among atrial fibrillation patients].

Objective: To explore gender-specific factors and their contributions to ischemic stroke among atrial fibrillation (AF) patients. Methods: A case-control study was conducted. The relevant data were obtained from the database of China National Stroke Screening Survey. The cases were first-ever ischemic stroke cases diagnosed from September 2013 to September 2015. Frequency-matched for the age and distribution of city and country, controls were randomly selected by 1∶3 ratio from individuals with AF but without stroke in the program. Altogether, there were 85 male cases (320 controls) and 147 female cases (484 controls). Unconditional logistic regression model was applied for the analysis of relevant factors of the onset of ischemic stroke, and their population-attributable risk proportion [PARP, (95%CI)] was calculated. Results: The age of male subjects in the case group and control group were (65.26±11.20) and (64.83±11.08) years old, and that of females in two groups were (63.63±10.40) and (63.93±10.35) years old. According to the PARP (95%CI), relevant factors of the onset of ischemic stroke in a descending sequence were hypertension history [35.63 (18.64-47.73)], family history of stroke [28.70 (23.63-32.30)]and physical inactivity [15.73 [5.62-23.06)] among male AF patients, and family history of stroke (29.39 (24.21-33.08)), dyslipidemia (22.17 (2.26-36.45)) and smoking [2.09 (0.76-3.24)] among female AF patients. Conclusion: The relevant factors of ischemic stroke were different between male and female AF patients.

[A novel VSX1 gene mutation identified in a sporadic keratoconus patient from China].

Objective: To investigate the possibility of the visual system homeobox 1 (VSX1) gene as a candidate susceptibility gene for Chinese patients with sporadic keratoconus, and to identify sequence variants of the VSX1 gene in such patients. Methods: Cross-sectional study. Genomic DNA was extracted from the leukocytes in the peripheral venous blood of 50 patients with sporadic keratoconus and 50 control subjects without this ocular disorder. Five exons and the intron-exon splicing of the VSX1 gene were amplified by polymerase chain reaction (PCR). The PCR products were directly sequenced and compared to the GeneBank database to find mutations. Bioinformatics analysis was done to predict the influence of these mutations on proteins. Results: One novel missense heterozygous mutation (p.R131P) was found in exon 1 of the VSX1 gene in one keratoconus patient. Another heterozygous mutation (p.G160V) in exon 2 was found in two keratoconus patients. These mutations were not detected in the control subjects. Bioinformatics analysis predicted that the p.R131P mutation may not cause a pathogenic change, but the p.G160V mutation might be functionally deleterious. In intron 3 of the VSX1 gene, the nucleotide substitution of g.8326G>A was detected to be heterozygous in 3 cases of sporadic keratoconus and 4 cases of control and homozygous in 2 cases of sporadic keratoconus and 1 case of control. The variation of g.8326G>A belonged to a single polymorphism change of the VSX1 gene. Conclusions: The p.R131P detected in this study is a novel mutation of the VSX1 gene. Sequence variants of the VSX1 gene were identified for the first time in Chinese patients with sporadic keratoconus, but their precise role in disease causation requires further investigations. (Chin J Ophthalmol, 2018, 54: 212-217).

[Reproductive and developmental toxicity of 2- (2H-1, 2, 3-benzotriazol-2-yl) -4-methyl-6- (2-methylpropen-2-yl) phenol in mice: an experimental study].

Objective: To investigate the reproductive and developmental toxicity of 2- (2H-1, 2, 3-benzotriazol-2-yl) -4-methyl-6- (2-methylpropen-2-yl) phenol in mice and to provide a basis for its risk assessment. Methods: The reproductive and developmental toxicity of 2- (2H-1, 2, 3-benzotriazol-2-yl) -4-methyl-6- (2-methylpropen-2-yl) phenol was tested using the screening method of chemicals with reproductive and developmental toxicity in "Chemical Testing Method" (SEPA). After five days of adaptive feeding, 120 specific pathogen-free healthy Kunming mice (male/female ratio=1:1) were orally administered 0 (control) , 146, 292, and 584 mg/kg 2- (2H-1, 2, 3-benzotriazol-2-yl) -4-methyl-6- (2-methylpropen-2-yl) phenol for two weeks. One male mouse was mated with one female mouse in a single cage. The day on which a vaginal plug was observed was defined as gestation day 0 (GD0). The exposure for female mice was sustained to four days postpartum and the exposure for male mice was sustained for two weeks after mating. The body weight, food intake, body length, tail length, and sex ratio were recorded and the reproductive index was calculated. The reproductive organs were weighed and subjected to histopathological examination. Results: The 584 mg/kg group had significantly lower body weight at weeks 5 and 6 and food intake at week 6 in male mice, uterus weight and uterus/body weight ratio in female mice, and body weight, body length, and tail length on day 0 in offspring compared with the control group (all P<0.05). The 292 mg/kg group had significantly lower testis weight of male mice and food intake of female mice at gestational week 2 than the control group (both P<0.05). The 146 mg/kg group had significantly lower food intake of female mice at gestational week 2 than the control group (P<0.05) . Conclusion: For male and female Kunming mice, the no observed adverse effect levels of 2- (2H-1, 2, 3, -benzotriazol-2-yl) -4-methyl-6- (2-methylpropen-2-yl) phenol are both 146 mg/kg.

The demographics, treatment characteristics and quality of life of adult people with haemophilia in China - results from the HERO study.

INTRODUCTION: Haemophilia management in China needs to be further developed. To further improve the quality of life (QoL) of people with haemophilia (PWH) in China, it is important to investigate the peculiarities of China as compared to other countries. AIM: The primary objective of the Haemophilia Experiences, Results and Opportunities (HERO) project was to quantify the impact of key psychosocial factors affecting PWH. This article presents the demographics, treatment characteristics, and QoL of adult PWH in China as compared with the results of the other nine countries participating in the HERO study. METHODS: This was a web- (except in Algeria) and questionnaire-based survey conducted in 10 countries. RESULTS: A total of 110 adult PWH from China and 565 from other countries completed the questionnaire. Compared with other countries, respondents in China reported: lower rate of employment (45.6% vs. 63.1%); lower percentages of being treated by prophylaxis (4.1% vs. 36.8%), being treated always at home (27.8% vs. 54.3%) and following treatment recommendation as instructed (6.2% vs. 40.5%); greater difficulty in obtaining replacement factor products (97.3% vs. 29.6%) and visiting their treatment centre (60.9% vs. 26.4%); more annual bleeds requiring treatment (mean: 29.4/year vs. 15.4/year); lower mean self-evaluated disease control score (5.5 vs. 7.7), EQ-5D index (0.71 vs. 0.75) and visual analogue scale (7.1 vs. 7.5) scores. Employed PWH in China had a better self-reported generic QoL than those unemployed. CONCLUSIONS: The study suggests that there is a major need for further improvement of both medical care and ongoing psychosocial support for PWH in China.

[Preliminary evaluation of PET-CT and DWI for the detection of lymphoma bone marrow infiltration].

Objective: To evaluate the clinical value of PET-CT and DWI for the detection of bone marrow infiltration of lymphoma. Methods: The bone marrow samples of 93 untreated patients with pathologically diagnosed lymphoma were retrospectively analyzed. 61 patients underwent PET-CT examination, and other 32 underwent DWI examination. With bone marrow biopsy results as "gold standard" , the rates and sites of bone marrow infiltration of various lymphoma subtypes were analyzed, and the detection rates of the two imaging techniques were compared according to different lymphoma subtypes. Results: 39 patients were diagnosed as bone marrow infiltration based on pathological examination of bone marrow biopsies from routine sampling sites and bone marrow pathological examination of biopsies guided by PET-CT and DWI. The sensitivity, specificity, accuracy, positive and negative predictive values of PET-CT for lymphoma bone marrow infiltration were 80.8%, 88.6%, 85.3%, 84.0% and 86.1%, respectively; for DWI examination, these rates were 84.6%, 89.5%, 87.5%, 84.6% and 89.5%, respectively. The detection rates of the two imaging techniques for aggressive lymphoma were 37.5% (18/48) and 38.1% (8/21), respectively, which were slightly higher than those for the indolent lymphoma [23.1% (3/13) and 27.3% (3/11)], although the differences were not statistically significant (P=0.521, P=0.660). For both aggressive lymphoma and indolent lymphoma, the detection rates of DWI were numerically slightly higher than those of PET-CT(P=0.963, P=1.000). Conclusions: PET-CT and DWI have important and similar diagnostic value for bone marrow infiltration of lymphoma. None of PET-CT and DWI can replace bone marrow biopsy (BMB). However, image-guided bone marrow biopsies can improve the detection rate of bone marrow infiltration of lymphoma.

Physical properties and cellular responses to calcium phosphate coating produced by laser rapid forming on titanium.

In order to improve the surface bioactivity of titanium implants, CaCO3 and CaHPO4·2H2O powder was used to fabricate a calcium phosphate (CaP) coating using laser rapid forming (LRF) technology. The surface characterization showed that a porous and beta-tricalcium phosphate (beta-TCP) layer with small amount of alpha-TCP was formed on commercial pure titanium (Ti). The bonding strength between the coating and the Ti substrate was above 40.17 MPa measured by the means of pull-off test. The elastic modulus and the average microhardness of the coating were 117.61 GPa and 431.2 HV0.1, respectively. Through the static immersion test, it was proved that the coating could not only prevent the corrosion of Ti but also promote the redeposition of beta-TCP in artificial saliva. Osteoblasts possessed good attachment performance and strong proliferation ability on the surface of LRF coating (p < 0.05) in our cell experiments. This result demonstrated that the LRF coating could improve the surface cytocompatibility of titanium. Using scanning electron microscopy observation, it was found that osteoblasts grown on LRF coating formed multiple layers in pours. The result of reverse transcription PCR analysis demonstrated that the expressions of ITGß1 and BMP-2 were significantly (p < 0.05) upregulated on the LRF coating in a time-dependent manner, compared with uncoated Ti. These findings suggested that the LRF technology might be a promising potential treatment for fabricating CaP coatings on titanium implants.

Moving on income as a social determinant of health: free transit for social assistance recipients in Kingston, Ontario.

SETTING: The public health intervention setting is the City of Kingston, Ontario, Canada. The authors were involved in various stages of development of the intervention, including advocacy, design, implementation, and evaluation. INTERVENTION: In early 2017, the City of Kingston launched a pilot program to offer all recipients of social assistance a pass that would provide unlimited access to transit. The 1-year pilot program showed promise in terms of the objectives of the two departments involved, Housing and Social Services and Kingston Transit, as it reduced barriers to transportation and increased ridership in the city. The pilot was adopted as an ongoing program, The Ontario Works Universal Transit Pass, upon completion of the pilot. The program was funded by redirecting provincial means-tested and discretionary employment benefits from the Housing and Social Services budget to the Kingston Transit budget in order to purchase transit in bulk for Ontario Works (OW) recipients. OUTCOMES: The program provided greater access to essential services, increased household budgets, reduced stigma, and increased ridership. The improved social and economic opportunities that the program facilitated demonstrate the potential of addressing social determinants of health through transportation. IMPLICATIONS: The program illustrates an effective model for addressing income as a social determinant of health through transportation policy. Moreover, it demonstrates the potential for creative, cooperative approaches to inter/intra-government operations-like the transfer of funds from Housing and Social Services to Kingston Transit-which simultaneously promotes both greater efficacy of public services and health equity.

RéSUMé: CADRE: Le cadre de l'intervention en santé publique est la ville de Kingston, Ontario, Canada. Les auteurs étaient impliqués pendant les étapes variées d'intervention, y compris faire la promotion, la conception, la mise en œuvre, et l'évaluation. L'INTERVENTION: Au début de 2017, la ville de Kingston a lancé un projet pilote pour offrir à tous les bénéficiaires de l'aide sociale un laissez-passer qui fournirait l'accès illimité aux transports en commun. Le projet pilote dura un an et se montrait prometteur en termes des objectifs des deux services impliqués­Housing and Social Services (logement et services sociaux) et Kingston Transit (transports Kingston)­parce qu'il réduisait les barrières au transport et augmentait le nombre d'usagers de transports en commun en ville. Le projet a été adopté comme un projet continu, appelé le laissez-passer universel de transport en commun de L'Ontario au travail, dès l'achèvement du projet pilote. Le programme était financé en redirigeant les bénéfices d'emploi provincial disponibles avec l'évaluation des revenus, qui font parties du budget pour le service logement et services sociaux, vers le budget du service de transports au Kingston. Les finances étaient utilisées pour acheter les laissez-passer de transport en gros pour les bénéficiaires de L'Ontario au travail. RéSULTATS: Le programme fournissait un meilleur accès au services essentiels, augmentait les budgets famille, réduisait la stigmatisation, et augmentait le nombre d'usagers de transports en commun. Les opportunités économiques et sociales améliorées que le programme avait facilitées illustre le potentiel de s'occuper des facteurs déterminants sociaux de la santé à travers les transports en commun. CONSéQUENCES: Le programme démontre un modèle efficace pour s'occuper de revenu comme un facteur déterminant social de la santé à travers la politique des transports. En outre, il illustre le potentiel pour les approches créatives et coopératives aux opérations entre les niveaux gouvernementaux­comme le transfert des finances du service de logement et services sociaux vers le budget du service de transport au Kingston­qui provoque simultanément une efficacité plus grande des services publics ainsi que l'équité de la santé.

Isolation to stabilization: A Housing First approach to address homelessness in Kingston, Ontario.

SETTING: Homelessness is a significant and growing public health concern across Canada. In Kingston, Ontario, the number of people experiencing chronic homelessness has more than doubled from 136 people in 2020 to 296 in 2023. INTERVENTION: An emergency shelter-in-place hotel program was established in April 2020 to provide non-congregate shelter to people experiencing homelessness and vulnerable to SARS-CoV-2 infections. Beyond preventing COVID transmission, the unintentional consequence was that a population that experienced chronic homelessness reduced drug consumption and became stable. In 2022, with increased funding from the Ministry of Health and the City of Kingston, a new Housing First program was implemented to transition individuals from homelessness to long-term stable housing. OUTCOMES: Between November 2022 and June 2023, a total of 34 clients initiated the program. Of these clients, 10 completed the program and were successfully housed, 10 remained active participants, and 14 were discharged before completion. Strengths and challenges were identified. Diverse services provided to meet the population's needs and strong collaborations with various community partners were facilitating factors. Inadequate external resources, a lack of evening and prosocial activities, and outside peers (not part of the program) who influenced recovery plans were identified as challenges. IMPLICATIONS: This program illustrates that simultaneously integrating housing, community building, mental health, and addiction services is possible and provides an innovative way to stabilize this vulnerable population of people experiencing homelessness. Results from this program and the knowledge generated through implementation are being used to further scale up the program.

RéSUMé: LIEU: Le sans-abrisme est un problème de santé publique important et en croissance au Canada. À Kingston, en Ontario, le nombre de personnes aux prises avec le sans-abrisme chronique a plus que doublé entre 2020 et 2023, passant de 136 à 296 personnes. INTERVENTION: Un programme d'abri d'urgence à l'hôtel mis en place en avril 2020 fournit un abri non collectif aux personnes aux prises avec le sans-abrisme vulnérables aux infections par le SRAS-CoV-2. En plus de prévenir la transmission de la COVID, ce programme a eu un effet inattendu : la population aux prises avec le sans-abrisme chronique a réduit sa consommation de drogue et s'est stabilisée. En 2022, grâce à un financement accru du ministère de la Santé et de la Ville de Kingston, un nouveau programme (Logement d'abord) a été mis en œuvre pour faciliter la transition des personnes sans abri vers un logement stable à long terme. RéSULTATS: Entre novembre 2022 et juin 2023, 34 personnes se sont inscrites à Logement d'abord. Dix d'entre elles ont terminé le programme et ont été logées avec succès, 10 y participent encore activement, et 14 en sont sorties avant la fin. Nous avons cerné les forces et les limites du programme. Les facteurs favorables ont été la gamme de services fournis en réponse aux besoins de la population et les liens de collaboration solides avec divers partenaires associatifs. Les limites du programme ont été le manque de ressources externes, l'absence d'activités prosociales et en soirée et l'influence des pairs de l'extérieur (non inscrits au programme) sur les plans de rétablissement des usagères et des usagers. CONSéQUENCES: Ce programme montre qu'il est possible d'intégrer simultanément le logement, la solidarité sociale, la santé mentale et les services en toxicomanie, et que c'est un moyen novateur de stabiliser cette population vulnérable aux prises avec le sans-abrisme. Les résultats du programme et les connaissances apportées par sa réalisation serviront à le reproduire à plus grande échelle.

Caveolin-1 deficiency protects against mesangial matrix expansion in a mouse model of type 1 diabetic nephropathy.

AIMS/HYPOTHESIS: Glomerular matrix protein accumulation, mediated largely by resident mesangial cells (MCs), is central to the pathogenesis of diabetic nephropathy. We previously showed that caveolin (CAV)-1/caveolae mediate matrix upregulation by MCs in response to high glucose and TGFß, two important pathogenic mediators of diabetic glomerular sclerosis. Here, we evaluated the in vivo role of CAV-1/caveolae in the development of diabetic nephropathy. METHODS: Diabetes was induced in Cav1-knockout (KO) mice and their wild-type (WT) counterparts by streptozotocin injection. After 10 months, kidneys were evaluated for the development of nephropathy, including glomerular sclerosis and upregulation of matrix proteins. Parallel experiments assessing glucose-induced matrix upregulation were carried out in MCs isolated from KO mice. RESULTS: KO diabetic mice developed hyperglycaemia and renal hypertrophy, but were protected from developing albuminuria and glomerular sclerosis compared with WT mice. KO mice were significantly protected from the upregulation of glomerular collagen I, fibronectin, connective tissue growth factor (CTGF) and TGFß. In vitro, glucose induced collagen I A1 promoter activation and collagen I, fibronectin and CTGF protein upregulation in WT but not KO MCs. Re-expression of Cav1 in KO cells restored this response. CONCLUSIONS/INTERPRETATION: Cav1 deletion rendered significant protection from glomerular matrix accumulation and albuminuria in a mouse model of type 1 diabetes. These studies provide a foundation for the development of renal-targeted interference with CAV-1/caveolae as a novel approach to the treatment of diabetic nephropathy.

Suppression of hepatoma tumor growth by systemic administration of the phytotoxin gelonin driven by the survivin promoter.

UNLABELLED: Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. However, there is currently no effective therapy strategy in the clinical practice. Recombinant phytotoxin gelonin fused to other factors have been used to treat different cancers. But there have been no reports of gelonin gene therapy. In this study, we have constructed a recombinant plasmid which contained a tumor-specific survivin promoter to drive phytotoxin gelonin (pSur-Gel). And the cytotoxicity effects of pSur-Gel in HCC were also validated both in vitro and in vivo. The expression level of survivin was detected in different liver cancer cell lines and normal liver cell lines by western blot analysis, and a survivin promoter-driven green fluorescent protein (GFP) expression vectors (pSur-GFP) was also tested in liver cancer cell line HepG2 and normal liver cell line LO2. Moreover, phytotoxin gelonin expression experiment and cytotoxicity experiment of pSur-Gel was performed in HepG2 cells and LO2 cells in vitro. Furthermore, anti-tumor effect of pSur-Gel against HepG2 xenografts and toxicity of this gene were evaluated in the mice model. Finally, LDH release assay, apoptosis assay and immunoblot analyse LC3 conversion (LC3-I to LC3-II) were tested. We found that the expression of survivin protein was higher in liver cancer cell lines compared with the normal liver cells. Further study showed that the pSur-GFP and pSur-Gel was expressed specially in liver cancer cell other than in normal liver cells. pSur-Gel plasmid could effectively inhibit the proliferation of liver cancer cells (*P<0.05), and significantly repress the growth of HepG2 xenografts via intravenous in vivo (*P<0.05). Otherwise, compared to cytomegalovirus promoter-driven gelonin expression vectors (pCMV-Gel), no significantly systemic toxicity or organ injuries had been observed in pSur-Gel treated mice. Further studies revealed that the phytotoxin gelonin induced cell death might be mediated by apoptosis and the damage of cell membrane. Taken together, treating hepatocellular carcinoma with the pSur-Gel may be a novel and interesting cancer gene therapy protocol and is worthy of further development for future clinical trials. KEYWORDS: liver cancer, gelonin, survivin promoter, gene therapy.

Ets-1 regulates its target genes mainly by DNA methylation in human ovarian cancer.

Ovarian cancer is the second most common gynaecological cancer worldwide, and its molecular mechanism has not been completely understood. Ets-1 is a member of the Ets transcription family and can play important roles in the regulation of extracellular matrix remodelling, invasion, angiogenesis and drug resistance in several malignancies, including ovarian cancer. In the current study, we downloaded two datasets from Gene Expression Omnibus database and sought to explore the regulation mechanism of Ets-1 in ovarian cancer by computational analysis of gene expression profiles. Microarray analysis identified a total of 548 genes that were regulated by Ets-1 in ovarian cancer. Functional annotation of these genes revealed that Ets-1 may be involved in several biological processes, both physiological and pathological, such as system development, response to stimulus, vascular endothelial growth factor (VEGF) production, morphogenesis, cell proliferation, cell adhesion and signal transduction. Further, DNA methylation analysis of the DEGs found that 26.5% (145) of them were differentially methylated genes in ovarian cancer. Our results provide insight into the mechanism of Ets-1 regulating the transcription of its target genes in the complex and multistep process of ovarian cancer progression.

[Efficacy of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei].

Objective: To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP). Methods: In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS). Results: A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions: CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.