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ObjectiveChina’s abrupt exit from the zero-COVID policy in late 2022 led to a rapid surge in infections, overwhelming healthcare systems and exposing healthcare providers to intensified psychological pressures. This sudden shift exacerbated pandemic-related psychological issues, including fear, health anxiety, and emotional processing difficulties. This study aimed to unravel the relationships among pandemic fear, cyberchondria, and alexithymia following China’s exit from the zero-COVID policy.MethodsA multi-center cross-sectional survey was conducted among 4088 nurses from 43 public hospitals in China. The web-based survey comprised the Fear of COVID-19 Scale, Cyberchondria Severity Scale, and Toronto Alexithymia Scale. Network analysis was employed to explore the interconnections and identify central components within these psychological and behavioral constructs.ResultsThe analysis revealed a dense network with predominantly positive connections. Specific aspects of cyberchondria and pandemic fear exhibited the highest strength centrality, indicating their critical influence. The externally oriented thinking dimension of alexithymia emerged as a crucial bridge node, linking pandemic fear and cyberchondria. The network structure demonstrated consistency across diverse educational backgrounds and career stages.ConclusionThese findings highlight the need for targeted interventions focusing on key network components, particularly externally oriented thinking, to disrupt the detrimental cycle of pandemic fear and cyberchondria. Healthcare organizations should promote balanced objective fact-focused and problem-solving approaches while also fostering skills in emotional awareness and expression, thereby mitigating the risk of maladaptive pandemic fear responses and dysfunctional online health information-seeking behaviors.

Background: More than half the domestic population in China were infected with COVID-19 in two months after ending “zero-infection policy”, which severely overwhelmed frontline healthcare providers with stress and fear. However, there is no study to date investigating the associations between nurses' fear of pandemic and cyberchondria. This study aimed to 1) investigate the correlations between fear pandemic and cyberchondria among frontline nurses, and 2) discover its potential mechanism. Methods: A cross-sectional sample of frontline nurses (N = 8161) was recruited from 98 hospitals across China in February 2023. Participants were invited to complete an online, self-rated standardized questionnaire focused on pandemic fear, alexithymia, psychological distress, and cyberchondria. Environmental, clinical and socioeconomic information were collected for adjustment while conducting chain mediation analysis. Results: When other covariates were controlled, it was found that fear of the pandemic significantly contributed to cyberchondria (b = 0.58, 95%CI [0.56, 0.60], p

Abstract Background Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. Herein, we found that Apoptin induced a strong and lasting endoplasmic reticulum (ER) stress response, Ca2+ imbalance, and triggered the mitochondrial apoptotic pathway. The aim of this study was to explore the mechanisms by which Apoptin exhibited anti‐tumor effects in HepG‐2 cells. Methods The intracellular levels of calcium (Ca2+) were induced by ER stress and determined by electron microscopy, flow cytometry, and fluorescence staining. The mitochondrial injury was determined by mitochondrial membrane potential and electron microscopy. Western blotting was used to investigate the levels of key proteins in ER stress and the apoptotic pathway in mitochondria. The relationship between Ca2+ levels and apoptosis in Apoptin‐treated cells was analyzed using a Ca2+ chelator (BAPTA‐AM), flow cytometry, and fluorescence staining. We also investigated the in vivo effects of Ca2+ imbalance on the mitochondrial apoptotic pathway using tumor tissues xenografted on nude mice. Results This study showed that Apoptin induced a strong and long‐ lasting ER stress and injury, which subsequently led to an imbalance of cellular Ca2+ levels, a reduction in the mitochondrial membrane potential, a significant extent image in the mitochondrial structure, and an increase in the expression levels of Smac/Diablo and Cyto‐C. Conclusions In summary, Apoptin induced apoptosis in HepG‐2 cells via Ca2+ imbalance and activation of the mitochondrial apoptotic pathway. This study provided a new direction for antitumor research in Apoptin.

BackgroundAbnormal interstitial fluid accumulation remains the major cause for patients with heart failure (HF) to endure a myriad of distressing symptoms and a decline in their health-related quality of life (HRQoL). The lymphatic system is essential in regulating fluid balance within the interstitial compartment and has recently been recognized as an important target for the prevention and mitigation of congestion. This study aimed to investigate the effects of exercises in activating lymphatic system on symptom distress and HRQoL among patients with HF.Methods and resultsThis was a pre-determined, secondary analysis of the TOLF-HF [The-Optimal-Lymph-Flow for Heart Failure (TOLF-HF)] study, a two-arm pilot randomized controlled trial evaluating the preliminary effects of the lymphatic exercise intervention in enhancing interstitial decongestion among patients with HF. Participants were randomized to receive either a four-week TOLF-HF program in addition to standard care or standard care alone. The Chinese version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was employed to measure symptom distress and HRQoL before and after the intervention. Data analyses included descriptive statistics, the independent sample t-test, Pearson’s chi-square test, the Mann-Whitney U test, and covariance analysis. Of the 66 patients enrolled, 60 completed the study. The study results exhibited that the TOLF-HF intervention were effective in alleviating both physical and psychological symptom distress. The intervention group yielded significantly lower MLHFQ total scores in comparison to the control group. The odd ratio of achieving meaningful improvement in HRQoL in TOLF-HF group was 2.157 times higher than those in the control group.ConclusionsThe TOLF-HF program focusing on activating lymphatic system was effective in alleviating physical and psychological symptom distress as well as improving HRQoL for patients with HF. The tolerability, feasibility, and effectiveness of the TOLF-HF intervention make it a promising intervention for patients to manage HF.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier (ChiCTR2000039121).

Abstract Background Infection is one of the most common causes of death in patients with hematological malignancies during chemotherapy. Due to its special location, local warmth and humidity, repeated pollution with stool and urine, and characteristically wrinkled anatomical structure within which bacteria can hide, the perianal becomes a site with a high incidence of infection. Such infection also has a high recurrence rate and high mortality, increasing the economic burden of patients, delaying the time of treatment and reducing the quality of life. In severe cases, sepsis occurs and endangers the patient’s life. Previous studies have confirmed the effectiveness of povidone iodine (PI) in the prevention of perianal infection in patients with hematological malignancies during chemotherapy, but these reports have not documented in detail the adverse events associated with sitz bathing and the lack of randomized controlled trials of different concentrations of dilute povidone iodine sitz bathing. Therefore, the evidence is insufficient. Hence, the objective of this paper is to determine whether a povidone iodine diluent sitz bath can reduce the incidence of perianal infection compared with conventional perianal cleaning care and to observe the incidence of perianal infection, the severity of perianal infection, and the complications related to the sitz bath among groups treated with different concentrations of povidone iodine diluent, especially in high-risk patients prone to perianal infection, to screen for the optimal concentration. Methods The trial is designed as a single-center, parallel, randomized, controlled and intervention trial with four parallel groups, and a primary endpoint of perianal infection occurred after this hospitalization chemotherapy. Randomization will be performed as simple randomization with a 1:1:1:1 allocation. This study received full ethics committee approval. The first patient was enrolled on May 1, 2021. A total of 268 patients with hematological malignancies undergoing chemotherapy who have risk factors for perianal infection will be enrolled with informed consent and randomly allocated to one of the four arms receiving (1) perianal cleaning care (control group D), (2) 1:100 PI diluted sitz bath (intervention group A), (3) 1:200 PI diluted sitz bath (intervention group B), and (4) 1:300 PI diluted sitz bath (intervention group C). The primary endpoint of the trial was the incidence of perianal infection. The secondary endpoints of the study will be the results of anal swab bacterial culture, the severity of perianal infection, the incidence of perianal adverse events (dryness, peeling, pigmentation, burning sensation), and pain scores. The length of hospitalization in days and hospitalization expenses will be recorded. Safety will be assessed with consideration of all adverse and severe adverse events related to the study treatment. Discussion We hypothesized that patients with hematological malignancies during chemotherapy would benefit from a povidone iodine diluted sitz bath. This study will provide evidence-based recommendations for clinicians and nurses. Trial registration Chinese Clinical Trial Registry (registration ID: ChiCTR2000041073). Registered on December 17, 2020. The protocol version number is V1.0,20201217. http://www.chictr.org.cn/edit.aspx?pid=66044&htm=4

Abstract Background Apoptin, as a tumor-specific pro-apoptotic protein, plays an important anti-tumoral role, but its mechanism of autophagy activation and the interaction between autophagy and apoptosis have not been accurately elucidated. Here, we studied the mechanism of apoptin-induced apoptosis and autophagy and the interaction between two processes. Methods Using crystal violet staining and the CCK-8 assay, we analyzed the effect of apoptin in the inhibition of liver cancer cells in vitro and analyzed the effect of inhibiting liver cancer in vivo by establishing a nude mouse tumor model. Flow cytometry and fluorescence staining were used to analyze the main types of apoptin-induced apoptosis and autophagy. Subsequently, the relationship between the two events was also analyzed. Flow cytometry was used to analyze the effect of ROS on apoptin-mediated apoptosis and autophagy mediated by apoptin. The effect of ROS on two phenomena was analyzed. Finally, the role of key genes involved in autophagy was analyzed using gene silencing. Results The results showed that apoptin can significantly increase the apoptosis and autophagy of liver cancer cells, and that apoptin can cause mitophagy through the increase in the expression of NIX protein. Apoptin can also significantly increase the level of cellular ROS, involved in apoptin-mediated autophagy and apoptosis of liver cancer cells. The change of ROS may be a key factor causing apoptosis and autophagy. Conclusion The above results indicate that the increase in ROS levels after apoptin treatment of liver cancer cells leads to the loss of mitochondrial transmembrane potential, resulting in endogenous apoptosis and mitophagy through the recruitment of NIX. Therefore, ROS may be a key factor connecting endogenous apoptosis and autophagy induced by apoptin in liver cancer cells. Graphical abstract Video abstract

BackgroundGrief is a natural and individualized response to different losses, but if grief persists or becomes pathological, professional interventions are required. Grief and corresponding interventions have received increasing attention, as the related concepts have been incorporated into the DSM-5 and ICD-11. Therefore, we conducted a bibliometric analysis to explore the developments in the field of grief intervention research.MethodsArticles on grief interventions were systematically searched and screened from the Web of Science Core Collection. The retrieved data were analyzed and visualized using VOSviewer and Bibliometrix software for journals, authors, institutions, countries, references, and keywords.ResultsA total of 9,754 articles were included. The number of articles on grief interventions has increased significantly each year since 1990. Death Studies was the journal that published the most articles in this field. We identified 25,140 authors contributed to this research area and these authors were from 123 countries and 6,630 institutions. Boelen PA secured the first position in article production, Columbia University emerged as the most productive affiliation and the United States was the foremost leading in grief intervention research. The prevalent keywords utilized in this field comprised bereavement, grief, death, depression, and palliative care.ConclusionThe quantity of publications regarding grief interventions is increasing. Although most prior studies have focused on mortality, grief, and health, emerging themes such as COVID-19, grief among workers, and disfranchised grief have drawn increasing attention in recent years. Future studies may focus on investigating the complexities and challenges of grief, including its underlying mechanisms and impact on mental well-being.

BackgroundReversible splenial lesion syndrome (RESLES) is a rare neurological condition characterized by temporary abnormalities in the splenium of the corpus callosum, which has been reported in mental disorders. Previous studies on bipolar disorder (BD) primarily focused on aspects such as brain structure and function, neurochemical changes, and genetics. However, there have been no studies reporting the occurrence of this syndrome during hypomanic episodes and its disappearance during the remission phase in bipolar disorder type 2 (BD-II).Case presentationWe present a case report of a 30 years-old female patient with BD-II who exhibited symptoms of RESLES during a hypomanic episode. The patient, with a 12 years psychiatric history, has experienced recurrent depressive episodes initially, with the first hypomanic episode occurring 8 years ago. During this period, this patient made several visits to the outpatient clinic to have her medications adjusted due to repeated suicide attempts. This time, she was admitted to our hospital with a second hypomanic episode due to drug withdrawal during pregnancy. The RESLES was observed on her brain magnetic resonance image, and it was alleviated after treatment with lithium carbonate and quetiapine until achieving remission.ConclusionWe present the first report of identifying RESLES in BD-II with hypomanic episodes, which subsequently disappears during the remission phase. Our case report highlights a potential association between BD and RESLES, emphasizing the need for future studies to explore the underlying mechanisms connecting these two conditions in greater depth.

IntroductionHuman adenovirus type 7 (HAdv-7) infection is the main cause of upper respiratory tract infection, bronchitis and pneumonia in children. At present, there are no anti- adenovirus drugs or preventive vaccines in the market. Therefore, it is necessary to develop a safe and effective anti-adenovirus type 7 vaccine.MethodsIn this study, In this study, we used the baculovirus-insect cell expression system to design a recombinant subunit vaccine expressing adenovirus type 7 hexon protein (rBV-hexon) to induce high-level humoral and cellular immune responses. To evaluate the effectiveness of the vaccine, we first detected the expression of molecular markers on the surface of antigen presenting cells and the secretion of proinflammatory cytokines in vitro. We then measured the levels of neutralizing antibodies and T cell activation in vivo.ResultsThe results showed that the rBV-hexon recombinant subunit vaccine could promote DC maturation and improve its antigen uptake capability, including the TLR4/NF-κB pathway which upregulated the expression of MHCI, CD80, CD86 and cytokines. The vaccine also triggered a strong neutralizing antibody and cellular immune response, and activated T lymphocytes.DiscussionTherefore, the recombinant subunit vaccine rBV-hexon promoted promotes humoral and cellular immune responses, thereby has the potential to become a vaccine against HAdv-7.

BackgroundFluid overload remains a vexing problem in management of heart failure. The lymphatic system that plays the central role in fluid homeostasis has recently been explored as a potential target to counteract tissue fluid overload. The goal of the study was to evaluate the preliminary effects of exercises in activating lymphatic system on fluid overload symptoms, abnormal weight gains, and physical functions for patients with heart failure.Methods and resultsA pilot, pre- and post-test, randomized clinical trial was conducted to recruit a total of 66 patients who were randomized to receive either a 4-week The-Optimal-Lymph-Flow for Heart Failure (TOLF-HF) program or usual care alone. The primary outcome was the prevalence and burden of the fluid overload symptoms. Findings of the trial showed that the TOLF-HF intervention was effective in reducing the prevalence or burden of the majority of fluid overload symptoms. TOLF-HF intervention also demonstrated significant improvement in the outcomes of abnormal weight gains (MD: −0.82; 95% CI: −1.43 to −0.21; P = 0.010) and physical functions (F = 13.792, P

Betulinic acid is found in the several foods and plants, such as sour jujube fruits, papaya, persimmon, betulinic acid exhibits low toxicity and a wide range of anticancer activities. Ferritinophagy and ferroptosis are related to tumor formation and therapeutic effects, both of which are controlled by iron metabolism and inextricably linked. In this study, we discovered that betulinic acid could suppress proliferation and migration of hepatoma cells, raised ROS level and inhibited antioxidation level in cells. Ferrostatin-1 was used to determine the death way of hepatoma cells induced by betulinic acid. Betulinic acid could cause ferritinophagy-related phenomenon in vivo and in vitro, promote ferritinophagy-protiens expressions, induce ferritinophagy to inhibit tumours finally. In vivo studies revealed the low toxicity of betulinic acid in mice, the dose of human was about 10 times that of mice, the using dose of human could also be achievable. These findings illustrate the potential of betulinic acid for treatment of cancer.

Influenza viruses pose a serious threat to human health, infecting hundreds of millions of people worldwide each year, resulting in a significant increase in global morbidity and mortality. Influenza activity has declined at the onset of the COVID-19 pandemic, but the genetic diversity of B/Victoria lineage viruses has increased significantly during this period. Therefore, the prevention and treatment of the influenza B Victoria strain virus should continue to attract research attention. In this study, we found that Atractyloside A (AA), one of the effective components in Atractylodes lancea (Thunb.) DC shows potential antiviral properties. This study shows that AA not only possesses anti-influenza B virus infection effects in vivo and in vitro but also can regulate macrophage polarization to the M2 type, which can effectively attenuate the damage caused by influenza B virus infection. Therefore, Atractyloside A may be an effective natural drug against B/Victoria influenza infection.

Abstract Background Pressure dressings have been used after open hemorrhoidectomy to protect surgical wounds and manage postoperative bleeding for many years. However, pressure dressings may increase the incidence of postoperative complications, such as urinary retention, medical adhesive-related skin injury, and pain. A previous controlled trial included 67 patients who underwent Milligan-Morgan hemorrhoidectomy. The data indicated that the use of a nonpressure dressing after hemorrhoidectomy reduces the incidence of urinary retention and catheterization. However, the incidence of severe postoperative bleeding and other postoperative complications was not assessed. There is no consensus on whether it is necessary and beneficial to use a nonpressure dressing after hemorrhoidectomy. The results of this randomized clinical study will help answer this question. Methods In this study, we plan to include 186 patients who have undergone modified Milligan-Morgan hemorrhoidectomy, which only sutured external hemorrhoids to reduce the risk of bleeding. The purpose is to determine whether the use of nonpressure dressings after open hemorrhoidectomy is inferior to the use of pressure dressings in terms of severe postoperative bleeding and postoperative complications. The primary endpoints of the trial are the incidence of urinary retention within 24 h after surgery and the incidence of severe postoperative bleeding 1 h after dressing removal, which requires revision surgery within 24 h after the surgery. The secondary endpoints of the study are the pain score, anal distension score, postoperative use of analgesics, and incidence of medical adhesive-related skin injury, all of which will be assessed before removing the dressings. The length of hospitalization in days and hospitalization expenses will be recorded. Safety will be assessed with consideration of all adverse and severe adverse events related to the study treatment. Discussion The study received full ethics committee approval. The first patient was enrolled on 27 November 2020. The results of this trial will finally answer the question of whether a nonpressure dressing after open hemorrhoidectomy is necessary and beneficial. Trial registration Chinese Clinical Trial Registry ChiCTR2000040283 . Registered on 28 November 2020.

Pyroptosis is related to the occurrence, development, and therapeutic response of tumors, mediated by the proteins of the Gasdermin family. These proteins have become potential biomarkers for cancer treatment, and their agonists are likely to become a new direction in research and development of antitumor drugs. In this study, we found that myricetin has an inhibitory effect on lung cancer cells of the activation of pyroptosis. Analysis of the expression of Gasdermin family proteins revealed that this phenomenon was caused by the cleavage of GSDME. Subsequently, specific inhibitors, we found that caspase-3 was its upstream activation factor. In addition, mitochondrial and endoplasmic reticulum (ER) analysis showed that myricetin can cause endoplasmic reticulum stress and increase reactive oxygen species (ROS) levels. Subsequent inhibition of caspase-12 revealed that the expression levels of cleaved-caspase-3 and cleaved-GSDME were significantly reduced, resulting in the inhibition of pyroptosis. Using in vivo experiments, we also found that the treatment with myricetin can reduce tumor volume and significantly increase the level of pyroptosis-related proteins in tumor tissues. Overall, our findings show that myricetin induces cell death of lung cancer cells primarily through an ER stress pathway-induced pyroptosis. Therefore, myricetin has the potential to be used as a pyroptosis agonist in research and development of antitumor drugs.

Ferritinophagy is associated with tumor occurrence, development, and therapy effects. Ferritinophagy and ferroptosis are regulated by iron metabolism and are closely connected. LC3 protein is a key protein in autophagy. Following the binding of NCOA4 to FTH1, it links to LC3Ⅱ in lysosomes, a symbol of ferritinophagy. A ferritinophagy’s inducer is likely to open new avenues for anticancer medication research and development. In this study, we discovered that caryophyllene oxide has a substantial inhibitory effect on HCCLM3 and HUH7 cells, by regulating the level of cellular oxidative stress, and the levels of autophagy and iron metabolism in HCCLM3 and HUH7 cells, leading to a ferritinophagy-related phenomenon. Furthermore, the results of T-AOC, DPPH free radical scavenging rate, and hydroxyl radical inhibition indicated that caryophyllene oxide can inhibit cell anti-oxidation. The examination of the ferritinophagy-related process revealed that caryophyllene oxide promotes the production and accumulation of intracellular reactive oxygen species and lipid peroxidation. NCOA4, FTH1, and LC3Ⅱ were found to be targeted regulators of caryophyllene oxide. Caryophyllene oxide regulated NCOA4, LC3 Ⅱ, and FTH1 to promote ferritinophagy. In vivo, we discovered that caryophyllene oxide can lower tumor volume, significantly improve NCOA4 and LC3 protein levels in tumor tissue, and raise Fe2+ and malondialdehyde levels in serum. The compound can also reduce NRF2, GPX4, HO-1, and FTH1 expression levels. The reduction in the expression levels of NRF2, GPX4, HO-1, and FTH1 by caryophyllene oxide also inhibited GSH and hydroxyl radical’s inhibitory capacities in serum, and promoted iron deposition in tumor tissue resulting in the inhibition of tumor growth. In summary, our study revealed that caryophyllene oxide mostly kills liver cancer cells through ferritinophagy-mediated ferroptosis mechanisms. In conclusion, caryophyllene oxide may be used as a ferritinophagy activator in the field of antitumor drug research and development.

Ad-VT (Ad-Apoptin-hTERTp-E1a) is a type of oncolytic adenovirus with dual specific tumor cell death ability. It can effectively induce cell death of breast cancer cells and has better effect when used in combination with chemotherapy drugs. However, it has not been reported whether Ad-VT reduces the resistance of breast cancer cells to chemotherapy drugs. The purpose of this study is to investigate the effect of Ad-VT on drug resistance of Adriamycin-resistant breast cancer cells. For this, the effects of different doses of Ad-VT on the resistance of breast cancer cells to Adriamycin were analyzed using qualitative and quantitative experiments in vitro and in vivo. The Ad-VT can reduce the resistance of MCF-7/ADR to adriamycin, which is caused by the reduction of MRP1 protein level in MCF-7/ADR cells after treatment with Ad-VT, and MRP1 can be interfered with by autophagy inhibitors. Subsequently, the upstream signal of autophagy was analyzed and it was found that Ad-VT reduced the resistance of cells to doxorubicin by reducing the level of mTOR, and then the analysis of the upstream and downstream proteins of mTOR found that Ad-VT increased the sensitivity of MCF-7/ADR cells to adriamycin by activating AMPK-mTOR-eIF4F signaling axis. Ad-VT can not only significantly induce cell death in MCF-7/ADR cells, but also improved their sensitivity to Adriamycin. Therefore, the combination of Ad-VT and chemotherapy drugs may become a new strategy for the treatment of breast cancer in overcoming Adriamycin resistance.

Type 2 diabetic mellitus (T2DM), often accompanied by disorders of glucose and lipid metabolism, has troubled hundreds of millions of people. Xiaokeyinshui extract combination (XEC), derived from traditional Chinese medicines formula, has exerted hypoglycemic effects against T2DM. However, its mechanism of metabolic level is still unclear. In this study, a T2DM mice model, induced by a high sucrose/high fat diet combined with low-dose streptozotocin (STZ) injections, was adopted. The biochemical index was determined and a combination of metabolomics and lipidomics analyses of plasma were performed. The results showed that XEC increased secretion of insulin and level of HDL-C, decreased levels of FBG, HbA1c, TC, TG, LDL-C and repaired islet structure in diabetic mice. In addition, the metabolic profiles of plasma were analyzed and 54 potential biomarkers were screened out, mainly including carbohydrates, lipids and amino acids. These potential biomarkers were found to be correlated with the following pathways: galactose metabolism, fructose and mannose metabolism, TCA cycle, arachidonic acid metabolism, glycerolipid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and amino acid metabolism. In conclusion, we speculated that carbohydrate metabolism, lipid metabolism and amino acid metabolism played roles in the therapeutic mechanisms of XEC on T2DM.

In this study, we investigated the effects of Apoptin-induced endoplasmic reticulum (ER) stress on lipid metabolism, migration and invasion of HepG-2 cells, and preliminarily explored the relationship between endoplasmic reticulum stress, lipid metabolism, migration, and invasion. The effects of Apoptin on ER function and structure in HepG-2 cells were determined by flow cytometry, fluorescence staining and western blotting by assessing the expression levels of ER stress related proteins. The effects of Apoptin on HepG-2 cells’ lipid metabolism were determined by western blot analysis of the expression levels of triglyceride, cholesterol, and lipid metabolism related enzymes. The effects of Apoptin on HepG-2 cells’ migration and invasion were studied using migration and invasion assays and by Western-blot analysis of the expression of proteins involved in migration and invasion. The in vivo effects of endoplasmic reticulum stress on lipid metabolism, migration and invasion of HepG-2 cells were also investigated by immunohistochemistry analysis of tumor tissues from HepG2 cells xenografted nude mice models. Both in vitro and in vivo experiments showed that Apoptin can cause a strong and lasting ER stress response, damage ER functional structure, significantly change the expression levels of lipid metabolism related enzymes and reduce the migration and invasion abilities of HepG-2 cells. Apoptin can also affect HepG-2 cells’ lipid metabolism through endoplasmic reticulum stress and the abnormal expression of enzymes closely related to tumor migration and invasion. These results also showed that lipid metabolism may be one of the main inducements that reduce HepG-2 cells’ migration and invasion abilities.

BackgroundHeart failure (HF) imposes a substantial burden on patients and healthcare systems. Hospital-to-home transitional care, involving time-limited interventions delivered predominantly by nurses, was introduced to lighten this burden. This study aimed to examine the effectiveness and dose-response of nurse-led transitional care interventions (TCIs) on healthcare utilization among patients with HF.MethodsHealth-related databases were systematically searched for articles published from January 2000 to June 2020. We included randomized controlled trials (RCTs) that compared nurse-led TCIs with usual care for adults hospitalized with HF and reported the following healthcare utilization outcomes: all-cause readmissions, HF-specific readmissions, emergency department visits, or length of hospital stay. Random-effects meta-analysis, meta-regression analysis, and dose-response analysis were performed to estimate the treatment effects and explain the heterogeneity.ResultsTwenty-five RCTs including 8422 patients with HF were included. Nurse-led TCIs for patients with HF resulted in a mean 9% (RR = 0.91; 95% CI = 0.82 to 0.99; p = 0.04; I2 = 46%) and 29% (RR = 0.71; 95% CI = 0.60 to 0.84; p < 0.0001; I2 = 0%) reduction in all-cause and HF-specific readmission risks respectively compared to usual care. The interventions were also effective in shortening the length of hospital stay (MD = -2.37; 95% CI = -3.16 to -1.58; p < 0.0001; I2 = 14%). However, no significant reduction was found for emergency department visits (RR = 0.96; 95% CI = 0.84 to 1.10; p = 0.58; I2 = 0%). The effect of meta-regression coefficients on all-cause and HF-specific readmissions was not statistically significant for any prespecified trial-level characteristic. Dose-response analysis revealed that the HF-specific readmission risk decreased in a dose-dependent manner with the complexity and intensity of nurse-led TCIs.ConclusionsNurse-led TCIs were effective in decreasing all-cause and HF-specific readmission risks, as well as in reducing the length of hospital stay; however, the interventions were not effective in reducing the frequency of emergency department visits.

Patients with heart failure are subjected to a substantial burden related to fluid overload symptoms. Exercise can help the lymphatic system function more effectively to prevent fluid build-up in tissues and interstitium, thus potentially mitigating the symptoms due to fluid overload. The objective of this systematic review was to examine the effects of exercise-based interventions on fluid overload symptoms among patients with heart failure. MEDLINE, Embase, Cochrane Library, and CINAHL databases were systematically searched for relevant studies published from inception to August 2021. We included randomized controlled trials that compared exercise-based interventions of different modalities and usual medical care for adult patients with heart failure and reported the effects of interventions on any symptoms related to fluid overload. A random-effects meta-analysis was used to estimate the effectiveness, and a subgroup analysis and univariate meta-regression analysis were used to explore heterogeneity. Seventeen studies covering 1086 participants were included. We found robust evidence indicating the positive effect of exercises in dyspnea relief (SMD = −0.48; 95%CI [−0.76, −0.19]; p = 0.001); the intervention length also influenced the treatment effect (β = 0.033; 95%CI [0.003, 0.063]; p = 0.04). Initial evidence from existing limited research showed that exercise-based intervention had positive effect to alleviate edema, yet more studies are needed to verify the effect. In contrast, the exercise-based interventions did not improve fatigue compared with usual care (SMD = −0.27; 95%CI [−0.61, 0.06]; p = 0.11). Findings regarding the effects of exercises on bodily pain, gastro-intestinal symptoms, and peripheral circulatory symptoms were inconclusive due to limited available studies. In conclusion, exercise-based interventions can be considered as an effective nonpharmacological therapy for patients with heart failure to promote lymph flow and manage fluid overload symptoms. Exercise-based interventions seem to have very limited effect on fatigue. More research should investigate the mechanism of fatigue related to heart failure. Future studies with high methodological quality and comprehensive assessment of symptoms and objective measure of fluid overload are warranted.

This dataset is supplementary to our accepted article in Journal of Ethnopharmacology [1]. Xiaokeyinshui (XKYS) formula, an anti-diabetic formula, was recorded in many ancient Chinese medical books. Xiaokeyinshui extract combination (XEC) originated from this ancient formula, consisting extracts of four herbal drugs, i.e., Coptidis Rhizoma, Liriopes Radix, bitter melon, and Cassiae Semen. In this study, herb extracts were prepared and mixed, producing Xiaokeyinshui extract combination (XEC). The optimized formula of XEC was also investigated via uniform experimental design. Diabetes was induced in Kunming mice, using high-sugar-high-fat diet combined with injection of streptozotocin (STZ) intraperitoneally. Different formulae of XEC were intragastrically administered to diabetic mice for 28 days. Fasting blood glucose (FBG), oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), total cholesterol (TC), total triglyceride (TG) were measured to assess the anti-diabetic effects of each formula. Multivariate second degree polynomial model was applied in the fitting of metabolic parameters, and the extremum value of each regression model was calculated using grid algorithm. In addition, an optimized formula of XEC was subjected to validation experiment in mice model. This data could provide basis for a reasonable analysis for the optimization of the formula of XEC.

Apoptin is a protein that specifically induces apoptosis in tumor cells. The anti-tumorigenic functions of Apoptin, including autophagy activation and its interaction with apoptosis, have not been precisely elucidated. Here we investigate the main pathways of apoptin-mediated killing of human liver cancer cells, as well as its putative role in autophagy and apoptosis. The anti-proliferative effect of apoptin in liver cancer cells was analyzed in vitro by crystal violet staining and MTS detection, and also in vivo using a tumor-based model. The main pathway related to apoptin-induced growth inhibition in vitro was evaluated by flow cytometry and fluorescence staining. The relationship between apoptosis and autophagy on apoptin-treating cells was analyzed using apoptosis and autophagy inhibitors, mitochondrial staining, Annexin V-FITC/PI flow detection, LC3 staining, and western blotting. The effect of ROS toward the apoptosis and autophagy of apoptin-treating cells was also evaluated by ROS detection, Annexin V-FITC/PI flow detection, LC3 staining, and western blotting. Inhibition of apoptosis in apoptin-treating liver cancer cells significantly reduced the autophagy levels in vitro. The overall inhibition increased from 12 h and the effect was most obvious at 48 h. Inhibition of autophagy could increase apoptin-induced apoptosis of cells in a time-dependent manner, reaching its peak at 24 h. Apoptin significantly alters ROS levels in liver cancer cells, and this effect is directly related to apoptosis and autophagy. ROS appears to be the key factor linking apoptin-induced autophagy and apoptosis through the mitochondria in liver cancer cells. Therefore, evaluating the interaction between apoptin-induced apoptosis and autophagy is a promising step for the development of alternate tumor therapies.