Cancer-associated fibroblast infiltration in osteosarcoma: the discrepancy in subtypes pathways and immunosuppression.

Introduction: Osteosarcoma (OS), the primary malignant bone tumor, has a low survival rate for recurrent patients. Latest reports indicated that cancer-associated fibroblasts (CAFs) were the main component of tumor microenvironment, and would generate a variable role in the progression of tumors. However, the role of CAFs is still few known in osteosarcoma. Methods: The processed RNA-seq data and the corresponding clinical and molecular information were retrieved from the Cancer Genome Atlas Program (TCGA) database and processed data of tumor tissue was obtained from Gene Expression Omnibus (GEO) database. Xcell method was used in data processing, and Gene set variation analysis (GSVA) was used to calculates enrichment scores. Nomogram was constructed to evaluate prognostic power of the predictive model. And the construction of risk scores and assessment of prognostic predictive were based on the LASSO model. Results: This study classified Cancer Genome Atlas (TCGA) cohort into high and low CAFs infiltrate phenotype with different CAFs infiltration enrichment scores. Then TOP 9 genes were screened as prognostic signatures among 2,488 differentially expressed genes between the two groups. Key prognostic molecules were CGREF1, CORT and RHBDL2 and the risk score formula is: Risk-score = CGREF1*0.004 + CORT*0.004 + RHBDL2*0.002. The signatures were validated to be independent prognostic factors to predict tumor prognosis with single-factor COX and multi-factor COX regression analyses and Norton chart. The risk score expression of risk score model genes could predict the drug resistance, and significant differences could be found between the high and low scoring groups for 17-AAG, AZD6244, PD-0325901 and Sorafenib. Discussion: To sum up, this article validated the prediction role of CAF infiltration in the prognosis of OS, which might shed light on the treatment of OS.

Swimming exercise is a promising early intervention for autism-like behavior in Shank3 deletion rats.

INTRODUCTION: SHANK3 is an important excitatory postsynaptic scaffold protein, and its mutations lead to genetic cause of neurodevelopmental diseases including autism spectrum disorders (ASD), Philan McDermid syndrome (PMS), and intellectual disability (ID). Early prevention and treatment are important for Shank3 gene mutation disease. Swimming has been proven to have a positive effect on neurodegenerative diseases. METHODS: Shank3 gene exon 11-21 knockout rats were intervened by a 40 min/day, 5 day/week for 8-week protocol. After the intervention, the rats were tested to behavioral measures such as learning and memory, and the volume and H-spectrum of the brain were measured using MRI; hippocampal dendritic spines were measured using Golgi staining and laser confocal. RESULTS: The results showed that Shank3-deficient rats had significant deficits in social memory, object recognition, and water maze learning decreased hippocampal volume and number of neurons, and lower levels of related scaffold proteins and receptor proteins were found in Shank3-deficient rats. CONCLUSION: It is suggested that early swimming exercise has a positive effect on Shank3 gene-deficient rats, which provides a new therapeutic strategy for the prevention and recovery of neurodevelopmental disorders.

Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy / 中国天然药物

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.

PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.

Understanding the dynamic relation between wastewater SARS-CoV-2 signal and clinical metrics throughout the pandemic

Wastewater surveillance (WWS) of SARS-CoV-2 was proven to be a reliable and complementary tool for population-wide monitoring of COVID-19 disease incidence but was not as rigorously explored as an indicator for disease burden throughout the pandemic. Prior to global mass immunization campaigns and during the spread of the wildtype COVID-19 and the Alpha variant of concern (VOC), viral measurement of SARS-CoV-2 in wastewater was a leading indicator for both COVID-19 incidence and disease burden in communities. As the two-dose vaccination rates escalated during the spread of the Delta VOC in Jul. 2021 through Dec. 2021, relations weakened between wastewater signal and community COVID-19 disease incidence and maintained a strong relationship with clinical metrics indicative of disease burden (new hospital admissions, ICU admissions, and deaths). Further, with the onset of the vaccine-resistant Omicron BA.1 VOC in Dec. 2021 through Mar. 2022, wastewater again became a strong indicator of both disease incidence and burden during a period of limited natural immunization (no recent infection), vaccine escape, and waned vaccine effectiveness. Lastly, with the populations regaining enhanced natural and vaccination immunization shortly prior to the onset of the Omicron BA.2 VOC in mid-Mar 2022, wastewater is shown to be a strong indicator for both disease incidence and burden. Hospitalization-to-wastewater ratio is further shown to be a good indicator of VOC virulence when widespread clinical testing is limited. In the future, WWS is expected to show moderate indication of incidence and strong indication of disease burden in the community during future potential seasonal vaccination campaigns. HighlightsO_LINeed to elucidate interpretation of CoV-2 WWS for seasonal vaccination campaigns. C_LIO_LIWWS to incidence relation weakens with peak natural and vaccination immunization. C_LIO_LIWWS to hospitalization remains strong with natural and vaccination immunization. C_LIO_LIWWS as indicator of hospitalization during future seasonal vaccination campaigns. C_LIO_LIWWS/hospitalization as indicator of VOC virulence with limited clinical testing. C_LI

Wastewater to clinical case (WC) ratio of COVID-19 identifies insufficient clinical testing, onset of new variants of concern and population immunity in urban communities

Clinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the extant and anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) is likely to have greater value as an important diagnostic tool to inform public health. As the widespread adoption of WWS is relatively new at the scale employed for COVID-19, interpretation of data, including the relationship to clinical cases, has yet to be standardized. An in-depth analysis of the metrics derived from WWS is required for public health units/agencies to interpret and utilize WWS-acquired data effectively and efficiently. In this study, the SARS-CoV-2 wastewater signal to clinical cases (WC) ratio was investigated across seven different cities in Canada over periods ranging from 8 to 21 months. Significant increases in the WC ratio occurred when clinical testing eligibility was modified to appointment-only testing, identifying a period of insufficient clinical testing in these communities. The WC ratio decreased significantly during the emergence of the Alpha variant of concern (VOC) in a relatively non-immunized communitys wastewater (40-60% allelic proportion), while a more muted decrease in the WC ratio signaled the emergence of the Delta VOC in a relatively well-immunized communitys wastewater (40-60% allelic proportion). Finally, a rapid and significant decrease in the WC ratio signaled the emergence of the Omicron VOC, likely because of the variants greater effectiveness at evading immunity, leading to a significant number of new reported clinical cases, even when vaccine-induced community immunity was high. The WC ratio, used as an additional monitoring metric, complements clinical case counts and wastewater signals as individual metrics in its ability to identify important epidemiological occurrences, adding value to WWS as a diagnostic technology during the COVID-19 pandemic and likely for future pandemics.

COVID-19 monitoring in rural communities: First comparison of lagoon and pumping station samples for wastewater-based epidemiology

Wastewater-based epidemiology/wastewater surveillance has been a topic of significant interest over the last year due to its application in SARS-CoV-2 surveillance to track prevalence of COVID-19 in communities. Although SARS-CoV-2 surveillance has been applied in more than 50 countries to date, the application of this surveillance has been largely focused on relatively affluent urban and peri-urban communities. As such, there is a knowledge gap regarding the implementation of reliable wastewater surveillance in small and rural communities for the purpose of tracking rates of incidence of COVID-19 and other pathogens or biomarkers. This study examines the relationships existing between SARS-CoV-2 viral signal from wastewater samples harvested from an upstream pumping station and from an access port at a downstream wastewater treatment lagoon with the communitys COVID-19 rate of incidence (measured as percent test positivity) in a small, rural community in Canada. Real-time quantitative polymerase chain reaction (RT-qPCR) targeting the N1 and N2 genes of SARS-CoV-2 demonstrate that all 24-hr composite samples harvested from the pumping station over a period of 5.5 weeks had strong viral signal, while all samples 24-hr composite samples harvested from the lagoon over the same period were below the limit of quantification. RNA concentrations and integrity of samples harvested from the lagoon were both lower and more variable than from samples from the upstream pumping station collected on the same date, indicating a higher overall stability of SARS-CoV-2 RNA upstream of the lagoon. Additionally, measurements of PMMoV signal in wastewater allowed to normalize SARS-CoV-2 viral signal for fecal matter content, permitting the detection of actual changes in community prevalence with a high level of granularity. As a result, in sewered small and rural communities or low-income regions operating wastewater lagoons, samples for wastewater surveillance should be harvested from pumping stations or the sewershed as opposed to lagoons.

Study on the synchronization of biventricular beats with the control mode of left ventricular assist device / 生物医学工程学杂志

Right ventricular (RV) failure has become a deadly complication of left ventricular assist device (LVAD) implantation, for which desynchrony in bi-ventricular pulse resulting from a LVAD is among the important factor. This paper investigated how different control modes affect the synchronization of pulse between LV (left ventricular) and RV by numerical method. The numerical results showed that the systolic duration between LV and RV did not significantly differ at baseline (LVAD off and cannula clamped) (48.52%

Food as medicine: A possible preventive measure against coronavirus disease (COVID-19).

The recent and ongoing outbreak of coronavirus disease (COVID-19) is a huge global challenge. The outbreak, which first occurred in Wuhan City, Hubei Province, China and then rapidly spread to other provinces and to more than 200 countries abroad, has been declared a global pandemic by the World Health Organization. Those with compromised immune systems and/or existing respiratory, metabolic or cardiac problems are more susceptible to the infection and are at higher risk of serious illness or even death. The present review was designed to report important functional food plants with immunomodulatory and anti-viral properties. Data on medicinal food plants were retrieved and downloaded from English-language journals using online search engines. The functional food plants herein documented might not only enhance the immune system and cure respiratory tract infections but can also greatly impact the overall health of the general public. As many people in the world are now confined to their homes, inclusion of these easily accessible plants in the daily diet may help to strengthen the immune system and guard against infection by SARS-CoV-2. This might reduce the risk of COVID-19 and initiate a rapid recovery in cases of SARS-CoV-2 infection.

Effect of Naikan cognitive therapy intervention on psychosomatic symptoms of female compulsory drug abuse addicts / 中华行为医学与脑科学杂志

Objective:To evaluate the intervention effect of Naikan cognitive therapy (NCT)on psychosomatic symptoms of female compulsory drug addicts.Methods:Seventy drug addicts who met the inclusion criteria and volunteered to participate in the study were selected and randomly divided into intervention group( n=35) and control group( n=35) with random number table method.The intervention group received 10 consecutive days of NCT, while the control group received the same period of mental health education.Before and after treatment, the two groups were assessed with symptoms check list-90(SCL-90), preceived social support scale(PSSS), simple coping style scale(SCSQ) and inclination of relapse questionnaire of drug rehabilitated addicts. Results:There was no significant difference between the two groups before the intervention (all P>0.05). Compared with pre-intervention, the total score of SCL-90((176.49±40.85) vs (152.60±31.17)), somatization, compulsion, interpersonal sensitivity, depression, anxiety, terror, paranoid and psychiatric factors were significantly decreased and the total scores of PSSS((59.09±14.60) vs (64.43±10.42)) family support, friend support and other support subscales increased significantly post-NCT intervention in the intervention group (all P<0.05). Compared with control group, the scores of positive coping((25.54±6.09) vs (22.37±7.04)) increased significantly, and the tendency of negative coping((8.20±3.59) vs (10.17±4.03)) and relapse((15.66±9.57) vs (22.11±10.18)) decreased significantly (all P<0.05) after intervention in the intervention group.There was no significant difference in the scores of all scales in the control group (all P>0.05). Conclusion:Naikan cognitive therapy can significantly improve the psychosomatic symptoms perceive social support and positive coping styles, and reduce the tendency of negative coping and relapse of female compulsory drug addicts.

Influence of EMT in Radiosensitivity of PC-9:an EGFR- mutant NSCLC cell line / 实用医学杂志

Objective To explore the influence of epithelial mesenchymal transition(EMT)in radiosensi-tivity of EGFR-mutant NSCLC cell with acquired resistance to EGFR-TKI. Methods In this study,EGFR-mutant human lung adenocarcinoma cell line PC-9 and Gefitinib acquired resistance cell line PC-9/AB were used. Western blot was used to assess EMT. Wound healing migration assay was tested. CCK8,colony formation and flow cytome-try were used to evaluate survival fraction ,as the sensitivity to irradiation. Results PC-9/AB displayed radioresis-tance(P<0.05). When EMT was reversed with CDH1,its radiosensitivity was significantly higher than PC-9/AB (P < 0.05). PC-9/TGF also displayed radioresistance (P < 0.05),as well as EMT phenotype presented. Conclusion EMT enhanced the radioresistance of EGFR-mutant NSCLC cell with acquired resistance to EGFR-TKI, possibly through TGF-βpathway.

The TNF-α/TNFR/NF-κB pathway in regulating alveolar macrophage apoptosis in coal workers' pneumoconiosis / 中国职业医学

OBJECTIVE: To study the mechanism of tumor necrosis factor( TNF)-α and its receptor( TNFR) signal transduction pathways in regulating cell apoptosis of alveolar macrophage( AM) in coal workers' pneumoconiosis( CWP).METHODS: Twenty-four coal workers with pneumoconiosis at stage Ⅰ were selected as CWP group and four observation subjects exposed to coal were chosen as observation group by using simple random sampling method. The bronchoalveolar lavage fluids of whole-lung lavage of two groups were collected. AMs were separated and purified. Then they were divided into 6 groups: a control group,a superoxide dismutase( SOD) group,a TNF/TNFR group,an anti-TNF-α antibody group,a Caspase-8 suppression group and a nuclear factor-κB( NF-κB) suppression group. The AMs of 6 groups with corresponding treatment were cultivated. After 24 hours,the cells were harvested and proteins extracted. The relative expression of TNF-α,TNFR1,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 protein was detected by Western blotting. RESULTS: The protein relative expression of TNF-α,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 in CWP group was significantly higher than those in the observation group( P < 0. 05). The protein relative expression of TNF-α,TNFR1,Caspase-8,Caspase-3 and NF-κB P50 in the TNF/TNFR group and the anti-TNF-αantibody group was lower than that of the control group( P < 0. 05). The above indexes in the anti-TNF-α antibody group were lower than that of the NF-κB suppression group( P < 0. 05). The protein relative expression of TNFR1,Caspase-8and Caspase-3 in the TNF/TNFR group was higher than that of the SOD group and the Caspase-8 suppression group( P <0. 05). The protein relative expression of TNFR1,Caspase-8 and NF-κB P50 in the TNF/TNFR group was lower than that of the NF-κB suppression group( P < 0. 05). Among the CWP patients,the relative expression of TNFR2 and NF-κB P65 in the TNF/TNFR group was lower than that of the control group( P < 0. 05),and higher than that of the SOD group( P <0. 05). CONCLUSION: AM apoptosis mediated by TNF-α/TNFR/NF-κB signal transduction pathway plays an important role in the occurrence and development of CWP. The TNF-α/TNFR/NF-κB signal transduction pathways inhibited or blocked at different stages can affect the expression of proteins related to AM apoptosis.

The relationships of hyperuricemia with clinical and Oxford classiifcations in children with IgA nephropathy / 临床儿科杂志

Objective To investigate the relationships of hyperuricemia with clinical and Oxford classifications in children with IgA nephropathy.Methods Clinical data of 213 children with IgA nephropathy were retrospective analyzed. According to the levels of blood uric acid, these children were divided into two groups, hyperuricemia group (n?=?51) and normal uric acid group (n?=?162). Differences of clinical index and Oxford classiifcation between the two groups were observed. Results The 24 h urinary protein, level of serum creatinine, glomerular ifltration rate (eGFR) in hyperuricemia group were signiifcantly higher than those in normal group (P all?

[A retrospective cohort study of 320 thousand subjects of colorectal cancer screening in Haining City].

OBJECTIVE: To evaluate the colorectal cancer incidence among compliers and non-compliers in the population of colorectal cancer screening area, and to provide scientific basis for health economic evaluation of cancer screening. METHODS: By screening different years build queue, to retrospectively compare the data of colorectal cancer screening from January 1, 2008 to December 31, 2013 and the data of cancer registration, and to analyze the colorectal cancer incidence rates among screening compliers and non-compliers, and to compare the average intervals between the end of screening and clinical cancer diagnosis using SPSS 19 statistical software. Mantel-Haenszel test was performed with a statistical significance level of α = 0.05. RESULTS: The non-compliance rate was 38.24% among males and 28.49% among females (P < 0.001). The non-compliance rate was highest in the 40-44 and 70-74 years age groups and lowest in the 50-59 years age group. The compliers of the screening were followed up for 476,049 person-years, and there were 51 cases of colorectal cancer, with an incidence rate of 10.71/100,000. The non-compliers of the screening were followed up for 259 183 person-years, and there were 66 cases of colorectal cancer, with an incidence rate of 25.46/100,000, which was 1.38 times higher than that of the compliance group (χ2 = 21.699, P < 0.001). The incidence rate of colorectal cancer among subjects who were positive in initial screening but refused to receive an electronic colonoscopy was as high as 164.40/100,000, and the average delay time was 20.8 ± 16.8 months. CONCLUSIONS: The colorectal cancer screening adherence among women is better than among men, and that of 50-54 years and 55-59 years age groups is better than in other age groups. The subsequent incidence rate of colorectal cancer in the non-compliance group is significantly higher than that of the compliance population.

Synthesis and anti-inflammatory activity of p-(sulfamyl) benzylidene-linked heterocyclic ketone derivatives / 中国药科大学学报

Aim: To study the synthesis and anti-inflammatory activity of p-(sulfamyl) benzylidene-linked hetero-cyclic ketone derivatives. Methods: A series of p-(sulfamyl) benzylidene-linked heterocyclic ketone derivatives were synthesized. Anti-inflammatory activity was evaluated against xylene-induced ear oedema in mice and against carrageenan-induced paw oedema in rats. Gastrointestinal side effects in the rats were also examined after continu-ous introgastric administration of these compounds once daily for 7 days. Results: Twelve compounds( LHZ-101-LHZ-112) were synthesized and their structures were confirmed by IR, ~1H NMR, MS and elemental analysis. LHZ-105, LHZ-106 and LHZ-111 exhibited marked anti-inflammatory activity in xylene-induced mice ear swelling model. LHZ-106 and LHZ-111 showed significant anti-inflammatory activity in carrageenan-induced rat paw ede-ma model. LHZ-105, LHZ-106 and LHZ-111 had less gastrointestinal side effects than diclofenac sodium and CI-1004. Conclusion: These results suggest that some of these compounds have the potential for anti-inflammatory activity with few gastrointestinal side effects.

Analysis on Antihypertensive Use from2002to2004in50Hospitals in Guangdong Province / 中国药房

OBJECTIVE:To evaluate the situation and the tendency of antihypertensive use in guangdong province.METHODS:The sales volume,defined daily use(DDDs)and daily expense of antihypertensive from2002to2004in guangdong province were investigated and analyzed.RESULTS:The sales volume of antihypertensive from2002to2004had been in?creasing.Calcium antagonist dominated over all other antihypertensives in respect of sales volume and DDDs.CONCLUSION:Calcium antagonist dominate in the antihypertensive market in guangdong province.