A Strategy Formulation Framework for Efficient Screening during the Early Stage of a Pandemic.

For viruses that can be transmitted by contacts of people, efficiently screening infected individuals is beneficial for controlling outbreaks rapidly and avoiding widespread diffusion, especially during the early stage of a pandemic. The process of virus transmission can be described as virus diffusion in complex networks such as trajectory networks. We propose a strategy formulation framework (SFF) for generating various screening strategies to identify influential nodes in networks. We propose two types of metrics to measure the nodes' influence and three types of screening modes. Then, we can obtain six combinations, i.e., six strategies. To verify the efficiencies of the strategies, we build a scenario model based on the multi-agent modelling. In this model, people can move according to their self-decisions, and a virtual trajectory network is generated by their contacts. We found that (1) screening people will have a better performance based on their contact paths if there is no confirmed case yet, and (2) if the first confirmed case has been discovered, it is better to screen people sequentially by their influences. The proposed SFF and strategies can provide support for decision makers, and the proposed scenario model can be applied to simulate and forecast the virus-diffusion process.

An empirical study of the effect of a flooding event caused by extreme rainfall on preventive behaviors against COVID-19.

Since the outbreak of COVID-19, wearing masks, vaccinations, and maintaining a safe distance has become social behaviors advocated by the government and widely adopted by the public. At the same time, unpredictable natural disaster risks brought by extreme climate change compound difficulties during epidemics and cause systemic risks that influence the existing pattern of epidemic prevention. Therefore, it is necessary to explore the effect of natural disaster risk caused by climate change on the response to outbreaks in the context of the COVID-19 epidemic. This study will focus on individual-level epidemic prevention behaviors, taking as an example the significant risk of severe destructive flooding caused by heavy rains in Henan, China, on July 20, 2021, which claimed 398 lives, to explore the effect of floods on the preventive behaviors of residents in the hardest hit areas against COVID-19. Through the multi-stage stratified random sampling of the affected residents in Zhengzhou, Xinxiang, Hebi, Luoyang, Anyang, and other cities in Henan Province, 2,744 affected people were surveyed via questionnaires. Through the linear regression model and moderating effect analysis, the study found that after floods, the individual's flood risk perception and response behaviors significantly correlated with the individual's prevention behaviors against COVID-19. Specifically, both flood risk perception and response behaviors strengthened the individual's prevention behaviors. Furthermore, the study also found that community risk preparation behavior and social capital can moderate the above relationship to a certain extent. The research can guide risk communication under the compound risk scenario and prevent risky public behavior under the consistent presence of COVID-19 in the community.

Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling.

Osteoporosis is a systemic bone metabolism disorder, which increases the risk of fractures, and in severe cases it may cause disability or even death. An important factor contributing to osteoporosis is the imbalance between bone formation and resorption. Naringin was reported to promote osteoblast differentiation, thus enhancing bone formation and alleviating osteoporosis development. However, the signalling pathways related to the regulatory mechanism of naringin in osteoporosis development are not clear. Proliferation of bone mesenchymal stem cells (BMSCs) treated with naringin in vitro was detected by CCK-8. An osteogenesis differentiation medium supplemented with naringin was applied to explore the effects of naringin on BMSC osteogenic differentiation, as detected by Alizarin red staining. Ovariectomy (OVX)-induced postmenopausal osteoporosis (PMOP) rats were orally administered with naringin. Dual-energy X-ray absorptiometry (DEXA) and micro-CT were applied to measure bone mineral density (BMD), bone volume/total volume (BV/TV), trabecula thickness (Tb.Th), trabecula number (Tb.N), trabecular separation (Tb.Sp) and bone surface/bone volume (BS/BV). H&E staining was performed to show pathological changes of the femur in PMOP rats after naringin treatment. Bone metabolism indicators were assessed by ELISA. We found that naringin suppressed the activation of the JAK2/STAT3 pathway. Naringin promoted BMSC proliferation and osteogenic differentiation. Furthermore, naringin alleviates bone loss and improves abnormal bone metabolism of PMOP rats. Collectively, naringin promotes BMSC osteogenic differentiation to ameliorate osteoporosis development by targeting JAK2/STAT3 signalling.

Efficacy of dydrogesterone on treating recurrent miscarriage and its influence on immune factors: a systematic review and meta-analysis.

BACKGROUND: This study aimed to explore the clinical efficacy of dydrogesterone in treating recurrent spontaneous abortion (RSA), analyze the influence of dydrogesterone on cellular immune factors, and provide evidence for clinical medication. METHODS: We used the China National Knowledge Infrastructure (CNKI) platform, Wanfang Data resource, PubMed, Web of Science, and Embase database to conduct a literature search to screen clinical studies published between 2005 and 2021 concerning dydrogesterone treatment for RSA. Stata 16.0 was used for meta-analysis and sensitivity analysis, and Begg's funnel chart was used to test publication bias. RESULTS: Only 13 studies, which included a total of 2,454 RSA patients, met the study inclusion criteria. The experimental group was treated with dydrogesterone, and the control group was treated with progesterone, human chorionic gonadotropin (hCG), placebo, or active immunization. Meta-analysis showed that the pregnancy success rate of the experimental group was higher than the control group, and the adverse reaction rate was lower than the control group. In addition, subgroup analysis also revealed that the experimental group had a higher pregnancy success rate than the control group and a lower adverse reaction rate. Levels of progesterone and hCG in the experimental group were dramatically higher than the control group after treatment. The experimental group also had higher levels of interleukin 4 (IL-4) and interleukin 10 (IL-10) than the control group, while levels of interferon-gamma (IFN-γ) were lower. DISCUSSION: Dydrogesterone, a safe and effective synthetic progesterone drug, had a significant clinical effect on RSA and effectively improved hormone levels and related cellular immune factors in RSA patients.

The Therapeutic Effect of Ge-Gen Decoction on a Rat Model of Primary Dysmenorrhea: Label-Free Quantitative Proteomics and Bioinformatic Analyses.

Ge-Gen decoction (GGD) is widely used for the treatment of primary dysmenorrhea (PD) in China. However, the mechanisms that underlie this effect are unclear. We investigated the protective mechanism of GGD in a rat model of PD using label-free quantitative proteomics. The model was established by the administration of estradiol benzoate and oxytocin. Thirty rats were divided into three groups (ten rats/group): a control group (normal rats), a model group (PD rats), and a treatment group (PD rats treated with GGD). The serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were measured by ELISA. Nanohigh-performance liquid chromatography-tandem mass spectrometry (nano-HPLC-MS/MS) was used to identify differentially expressed proteins (DEPs), and bioinformatics was used to investigate the protein function. Proteomic data were validated by western blot analysis. Oxytocin-induced writhing responses and abnormal serum levels of PGE2 and PGF2α were reversed following the administration of GGD. A total of 379 DEPs were identified; 276 were identified between the control group and the model group, 144 were identified between the model group and the treatment group, and 41 were identified as DEPs that were common to all groups. Bioinformatics revealed that the DEPs between the control group and the model group were mainly associated with cellular component biogenesis and binding processes. The DEPs between the model group and the treatment group were mainly involved in the protein binding and metabolic process. The expression levels of HSP90AB1 and the phosphorylation levels of ERK, JNK, and P-p38 in the uteri of rats in the three groups were consistent with the proteomic findings; MAP kinases (ERK, JNK, and p38) are known to be involved in the production of inflammatory cytokines and oxytocin signaling while HSP90AB1 is known to be associated with estrogen signaling. Collectively, these data indicate that GGD may exert its protective function on PD by regulating the inflammatory response and signaling pathways associated with oxytocin and estrogen.

Immunomodulatory activity-guided isolation and characterization of a novel polysaccharide from Atractylodis macrocephalae Koidz.

The Rhizoma of Atractylodis macrocephala Koidz. is a traditional Chinese herbal medicine that has been widely and empirically used for unexplained recurrent spontaneous abortion. In this study, a polysaccharide from the Rhizoma of Atractylodis macrocephala Koidz., designated as RAMP2, with an absolute molecular weight of 4.354 × 103 Da was isolated and found to be composed of mannose, galacturonic acid, glucose, galactose and arabinose. The NMR results displayed that →3-ß-glcp-(1→, →3,6-ß-glcp-(1→, →6-ß-glcp-(1→, T-ß-glcp-(1→, →4-α-galpA-(1→, →4-α-galpA-6-OMe-(1→, →5-α-araf-(1→, →4,6-ß-manp-(1→ and →4-ß-galp-(1→ were the main linkages in RAMP2. TEM and SEM results indicated that RAMP2 was globular in structure. Furthermore, in vitro experiments on murine CD4+ T cells revealed that RAMP2 could increase the percentage of Treg cells, up-regulate Foxp3, IL-10 and IL-2 mRNA expressions and the secretion of IL-10 and IL-2. RAMP2 was further shown to increase STAT5 phosphorylation levels in Treg cells, suggesting that RAMP2 increased the number of Treg cells through IL-2/STAT5 pathway.

Proteomic Analysis of Differentially Expressed Proteins in the Placenta of Anticardiolipin Antibody- (ACA-) Positive Pregnant Mice after Anzi Heji Treatment.

Anzi Heji (AZHJ) has been used to treat anticardiolipin antibody- (ACA-) positive pregnant women at risk of spontaneous abortion for many years. The aim of this study was to investigate the protective mechanism of AZHJ in a mouse model of ACA-positive pregnancy at risk of spontaneous abortion using label-free quantitative proteomics. Mice were divided into three groups: normal pregnant mice (control group), ACA-positive pregnant mice administered normal saline (model group), and ACA-positive pregnant mice administered AZHJ (AZHJ group). The model was established by injecting ß2-glycoprotein I (GPI) into mice for 18 days. The DEPs and their functions were analyzed by label-free quantitative proteomic and bioinformatic analyses. The levels of IL-6, IL-10, ACA, and TNF-α in the serum and placentas of the mice were measured by enzyme-linked immunosorbent assays (ELISAs). Proteomic data were validated by western blot analysis. The abnormal serum and placental levels of IL-6, ACA, and TNF-α in the model group were reversed by AZHJ. There were 39 upregulated and 10 downregulated DEPs in the AZHJ group relative to the model group. Bioinformatic analysis revealed that the DEPs were mainly involved in nucleic acid binding, signal conduction, and posttranslational modification. The placental levels of T-cell immunoglobulin mucin 3 (Tim-3) and Toll-like receptor 4 (TLR4) expression and AKT phosphorylation in the three groups were consistent with the proteomic findings. Tim-3/AKT signaling is involved in maternal-fetal immune tolerance, while TLR4 is associated with inflammatory responses. Collectively, these results indicate that AZHJ may exert its protective effect in ACA-positive pregnant mice by regulating the maternal-fetal immune tolerance and inflammatory response.

Delivery of paeonol by nanoparticles enhances its in vitro and in vivo antitumor effects.

Paeonol (Pae; 2'-hydroxy-4'-methoxyacetophenone) has attracted intense attention as a potential therapeutic agent against various cancers. However, the use of Pae is limited owing to its hydrophobicity. Recently, biodegradable polymeric nanoparticles with amphiphilic copolymers have been used as drug carriers; these have better bioavailability and are promising tumor-targeted drug delivery systems. In the current study, we prepared Pae-loaded nanoparticles (Pae-NPs) with amphiphilic block copolymers using nanoprecipitation. The physiochemical characteristics and antitumor effects of nanoparticles were evaluated in different cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed substantial inhibition of cell growth by Pae-NPs. Moreover, lower doses of Pae-NPs inhibited cell growth more efficiently than the equivalent doses of free Pae. Inhibition was characterized by significant elevation of intracellular reactive oxygen species and subsequent inhibition of Akt and regulation of apoptotic proteins, which could be partly reversed by pretreatment with the antioxidant N-acetylcysteine. In vivo results also demonstrated that Pae-NPs could exert much stronger antitumor effects than free Pae. Therefore, Pae-NPs represent a promising delivery system to overcome the low solubility of Pae and enable its use in treating cancer.

Modulation of an aqueous extract of Chinese medicine prescription Anzi Heji () on ratio of CD4+CD25+FOXP3+ regulatory T cells in anticardiolipin antibody-positive patients with threatened abortion.

OBJECTIVE: To evaluate Chinese medicine prescription, Anzi Heji (, AZHJ), on immune regulation of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in anticardiolipin antibody (ACA)-positive patients with threatened abortion. METHODS: Twenty-seven ACA-positive female patients with threatened abortion in the study group were treated with an aqueous extract of AZHJ 125 mL, twice daily for 4 consecutive weeks. The results were compared with control group composed by 15 healthy pregnant women. The ratio of CD4+CD25+FOXP3+ Treg in peripheral blood was identified by flow cytometry. The indicators of ACA were detected by enzyme-linked immunosorbent assay, and embryo development was checked by B-ultrasound. RESULTS: Compared with the control group, the ratio of CD4+CD25+FOXP3+ Treg cells in the study group was significantly lower before AZHJ treatment (P<0.01) and significantly increased after AZHJ treatment (P<0.01). After treatment, 20 of 27 patients (85%) showed that ACA indicators turned into negative, and 7 cases of quantitative indicators of ACA titers were significantly decreased (P<0.01). Total efficiency of treating miscarriage by AZHJ was 92.59%. CONCLUSION: AZHJ can regulate the immune function of pregnant women by increasing number of CD4+CD25+FOXP3+ Tregs.

Expression of Lysine-specific demethylase 1 in human epithelial ovarian cancer.

BACKGROUND: Lysine-specific demethylase 1(LSD1) is implicated in the tumorigenesis and progression in various cancers. However, the expression of LSD1 in epithelial ovarian cancer and its clinical significance has not been examined in detail. METHODS: Immunohistochemical was used to detect the expression of LSD1 in normal ovarian epithelial tissues, cystadenoma, borderline cystadenoma, and cystadenocarcinoma. Next, the correlations between expression of LSD1 and clinicopathological features was assessed in 96 species of serous cystadenocarcinoma and 36 species of mucinous cystadenocarcinoma. RESULTS: Immunohistochemical results showed that the expression of LSD1 was gradually increased from benign cystadenoma and borderline cystadenoma to cystadenocarcinoma. The positive ratio of LSD1 expression was 50% in normal ovarian epithelial tissues, 72% in serous cystadenoma, 73% in mucinous cystadenoma, 82% in borderline serous cystadenoma, 83% in borderline mucinous cystadenoma, 94% in serous cystadenocarcinoma and 92% in mucinous cystadenocarcinoma, respectively. LSD1 expression levels were associated with International Federation of Gynecology and Obstetrics stage and lymphatic metastasis in both serous and mucinous cystadenocarcinoma samples. Kaplan-Meier curves suggested that overall survival time of patients with high LSD1 expression was significantly shorter than that of patients with low LSD1 expression. Multivariate Cox proportional hazard regression indicated that higher LSD1 expression was a significant independent predictor of poor survival of EOC patients (P = 0.016). CONCLUSIONS: These results suggest that LSD1 may be involved in carcinogenesis and progression with promising therapeutic potential for epithelial ovarian cancer.