Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Can laparoscopic surgery be the preferred strategy for gallbladder cancer?]

Gallbladder cancer, notoriously known for its high malignancy, predominantly requires radical surgery as the treatment of choice. Although laparoscopic techniques have become increasingly prevalent in abdominal surgeries in recent years, the progress of laparoscopic techniques in gallbladder cancer is relatively slow. Due to the anatomical complexity, technical difficulty, and biological features of gallbladder cancer that is prone to metastasis and dissemination, traditional open surgery is still the main surgical approach. This study aims to reappraisal the current state of laparoscopic surgery for gallbladder cancer by appraising clinical practice and research evidence. Laparoscopic surgery for various stages of gallbladder cancer, including early, advanced, incidental, and unresectable gallbladder cancer were discussed. The promise and limitations of laparoscopic techniques are systematically explored.

Changes in menopausal symptoms comparing oral estradiol versus transdermal estradiol.

OBJECTIVE: This study aimed to compare the efficacy and safety of oral and transdermal estradiol in alleviating menopausal symptoms. METHOD: A total of 257 recently menopausal women were randomized into two groups. The t-E2 group received transdermal estradiol (2.5 g per day) (n = 128) and the o-E2V group received oral estradiol valerate (2 mg per day) (n = 129) for 24 weeks; both groups received micronized progesterone (200 mg per day). The primary outcome measure is the change in the modified Kupperman Menopausal Index (KMI) after 24 weeks of treatment. Menopausal symptoms were recorded at screening and at 4, 12 and 24 weeks using both the KMI and the Menopause Rating Scale (MRS). RESULTS: Significant amelioration was observed by KMI and MRS scores for both groups after treatment (p < 0.001). The mean KMI scores showed no difference between the two groups. The mean MRS scores were similar between the two groups at baseline and after 4 weeks of treatment. The results showed statistical differences after 12 weeks and 24 weeks of treatment (p = 0.005 and p = 0.011). Both the after-treatment scores minus the baseline scores of KMI and MRS and the incidence of adverse effects showed no difference between the two groups. CONCLUSIONS: This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and safety. CLINICAL TRIAL NUMBER: ChiCTR2300073146.

The WHO claims estrogens are 'carcinogenic': is this true?

Estrogens are in the list of carcinogenic chemicals from the World Health Organization (WHO). However, estrogens require additional factors such as stromal factors or progestogens to increase the ratio of proliferation/apoptosis for initiation of replication errors and consequent mutations to occur. These mutations require at least 5-10 years to develop into clinically detectable cancer, whereby this review is focused on breast cancer. The US National Cancer Institute highlighted a second mechanism of carcinogenicity: certain estrogen metabolites are capable of inducing DNA damage, even in low concentration. They can be assessed in the tissue and circulation. However, those deleterious reactions require excessive unrestricted oxidative cell stress, for example in industrial areas with heavy pollution. We have shown that this can be avoided using transdermal instead of oral estradiol treatment, especially important in smokers. The spectrum of metabolites is also influenced by other exogenous factors such as nutrition, physical activity and certain diseases. Reduction of breast cancer risk as demonstrated in the Women's Health Initiative (WHI) was explained by pro-apoptotic estrogen effects working after a certain 'time gap'. In addition, certain estrogen metabolites are carcinoprotective, if no genetic polymorphisms would impair their beneficial activities. Thus, since additional factors are required for both main pathways of carcinogenicity and because estrogens can even have carcinoprotective effects, we cannot agree with the statement from the WHO.

PGRMC1 promotes triple-negative breast cancer cell growth via suppressing ferroptosis.

OBJECTIVE: Triple-negative breast cancer (TNBC) is the most malignant form of breast cancer with increasing incidence and mortality worldwide. The progesterone receptor membrane component-1 (PGRMC1) is a well-identified hormone receptor with unknown functions in TNBC. The current study aims to explore the involvement of PGRMC1 in regulation of glutathione metabolism and ferroptosis during development of TNBC, providing new therapy options for TNBC patients. METHODS: Bioinformatic analysis, cell proliferation assay, western blot assay and other biochemistry methods were performed in TNBC cells. RESULTS: Our results revealed that the expression of PGRMC1 is higher in TNBC than the other subtypes of breast cancer. Interestingly, as an iron binding protein, increased PGRMC1 expression in TNBC cells leads to resistance to ferroptosis inducer. On the contrary, silenced PGRMC1 expression enhanced sensitivity of MDA-MB231 cells to Erastin. Mechanistically, overexpression of PGRMC1 decreased the intracellular free iron concentration, which was reduced by AG205 treatment. CONCLUSIONS: PGRMC1 increases the possibility of TNBC development through binding to intracellular iron and suppressing ferroptosis, providing the molecular basis of combined treatment for TNBC.

Expert consensus on fertility preservation in hematopoietic stem cell transplantation in girls in China.

Aims: Preconditioning before hematopoietic stem cell transplantation (HSCT) seriously damages the ovarian function and causes female infertility. This consensus focuses on the fertility preservation(FP) for girls needing HSCT, aim to make doctors in different disciplines aware of the importance, necessity and technique of ovarian protection.Materials and methods: Summarizing relevant literature and organizing multidisciplinary experts, including obstetrics and gynecology, reproductive medicine, oncology, pediatrics and hematology for full discussion.Results: Individuals exposed to HSCT in childhood are at higher risk of loss of fertility. Considering the high risk of premature ovarian insufficiency (POI) after conditioning and negative impact of POI on fertility, physical and mental health, it is absolutely necessary to protect fertility before HSCT conditioning. Ovarian tissue cryopreservation is the main fertility preservation option for these population.Conclusions: Fertility preservation before HSCT conditioning is crucial. Ovarian tissue cryopreservation is often the only option for these population.

Overexpression of miR-181a regulates the Warburg effect in triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancer (TNBC) is highly aggressive and leads to a poor prognosis. microRNA-181a (miR-181a) exhibits strong antineoplastic effects in many types of cancer. In this study, we examine the responses of human miR-181a-transfected TNBC cells and explore the mechanisms underlying the observed effects. METHODS: A series of cellular assays were conducted using cells from the MDA-MB-231 TNBC line to assess the impact of miR-181a overexpression. The extracellular acidification rate, lactate production and glucose uptake were evaluated as a measure of aerobic glycolysis (i.e. the Warburg effect). The expressions of glycolysis-related gene were analyzed. RESULTS: Viability, migration and survival of miR-181a-transfected MDA-MB-231 cells were all significantly reduced. miR-181a inhibited glycolysis in TNBC cells by reducing the rates of glucose uptake and lactate production and a substantial downregulation of factors known to contribute to the Warburg effect, including the serine/threonine kinase, AKT3, hypoxia-inducible factor-1α (HIF-1α) and progesterone receptor membrane component 1 (PGRMC1). CONCLUSION: Our results demonstrate that miR-181a may regulate glycolysis in MDA-MB-231 TNBC cells, potentially via interference with components of the AKT3-HIF-1α and PGRMC1 pathways. These results suggest that miR-181a might be developed as a therapeutic agent for use in antineoplastic regimens directed at TNBC and PGRMC1-overexpressing breast cancers.

[Risk factors of recurrence or metastasis in patients with medullary thyroid carcinoma].

Objective: To analyze the risk factors of recurrence or metastasis of medullary thyroid carcinoma (MTC) and the influencing factors of disease-free survival (DFS). Methods: The clinicopathological data of MTC patients who visited Tianjin Medical University Cancer Institute and Hospital and underwent surgery from August 2014 to August 2019 were retrospectively analyzed. The patients were divided into recurrence or metastasis group and no recurrence or metastasis group. Multivariate logistic regression analysis was used to analyze the risk factors for recurrence or metastasis. Kaplan-Meier survival analysis and Cox regression analysis were used to determine the risk factors of DFS. Results: A total of 158 MTC patients were enrolled in final analysis, including 83 females and 75 males, with a median age of 52 (19-74) years. There were 146 cases of sporadic MTC (92.4%) and 12 cases of familial MTC (7.6%), respectively. Bilateral thyroid lesions presented in 33 cases (20.9%) and multiple lesions presented in 57 cases (36.1%), respectively. The median follow-up time was 59.7 (10.0-93.0) months and the median DFS was 55.5 (0-92.9) months. Presence of multifocality, the largest tumor size>2 cm, T3/4, N1b, clinical stage Ⅲ/Ⅳ, lymph node metastasis ratio (LNR)>0.3, preoperative calcitonin>2 000 ng/L, postoperative calcitonin>40 ng/L and no biochemical cure were significantly correlated with the recurrence or metastasis and DFS of MTC (all P<0.05). Clinical stage Ⅲ/Ⅳ (OR=36.57, 95%CI: 1.33-1 006.98, P=0.033), the largest tumor size>2 cm (OR=5.81, 95%CI: 1.01-33.33, P=0.049), multifocality (OR=3.64, 95%CI: 1.03-12.88, P=0.045) and postoperative calcitonin>40 ng/L (OR=15.03, 95%CI: 1.39-162.61, P=0.026) were independent risk factors of recurrence or metastasis. Clinical stage Ⅲ/Ⅳ (HR=19.39, 95%CI:1.40-268.19, P=0.027), the largest tumor size>2 cm (HR=3.64, 95%CI: 1.02-13.02, P=0.047) and postoperative calcitonin>40 ng/L (HR=10.68, 95%CI: 1.34-84.95, P=0.025) were influencing factors for DFS (all P<0.05). Conclusion: The larger tumor size, advanced clinical stage and higher postoperative calcitonin at the initial treatment of MTC are risk factors for recurrence or metastasis and influencing factors for DFS.

[Correlation between dyslipidemia and the risk of papillary thyroid carcinoma].

Objective: To investigate the correlation between dyslipidemia and the risk of papillary thyroid carcinoma (PTC). Methods: A case-control study was conducted. PTC patients diagnosed by pathology in Tianjin Medical University Cancer Institute and Hospital from April 2014 to August 2019 were enrolled as the experimental group, and healthy controls in the physical examination center at the same time were also enrolled as the control group. The demographic data and blood lipid parameters of the subjects were collected. Multivariate logistic analyses were used to assess the correlation between dyslipidemia and the risk of PTC. Results: A total of 2 000 cases of PTC were enrolled, with a mean age of (42±12) years, including 1 419 females (71.0%) and 581 males (29.0%). There were 4 524 cases in the control group, with a mean age of (42±9) years, including 3 311 females (73.2%) and 1 213 males (26.8%). There was no statistically difference in age and gender between the two groups (both P>0.05). Compared with the control group, triglyceride (TG) [(1.7±1.1) vs (1.4±1.0) mmol/L, P<0.001] and low-density lipoprotein (LDL) [(2.9±0.8) vs (2.8±0.7) mmol/L, P=0.015] increased in peripheral blood of PTC patients, while high-density lipoprotein (HDL) [(1.3±0.4) vs (1.4±0.3) mmol/L, P<0.001] decreased, but the difference was not statistically significant in total cholesterol (TC) [(4.9±1.0) vs (4.9±0.8) mmol/L, P=0.172]. After adjusting for age and gender, increase of TC (OR=1.20, 95%CI: 1.06-1.34, P=0.003), TG (OR=1.73, 95%CI: 1.55-1.94, P<0.001), LDL (OR=1.21, 95%CI: 1.08-1.36, P=0.001), LDL/HDL (OR=1.77, 95%CI: 1.56-2.02, P<0.001) and decrease of HDL (OR=3.15, 95%CI: 2.78-3.58, P<0.001) were the related factors of PTC. Conclusions: Compared with the control group, patients with PTC have higher level of TG and LDL and lower level of HDL. Dyslipidemia is an important factor related to the risk of PTC.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

[Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis].

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

[Association of BMI with acute exacerbation in mild to moderate chronic obstructive pulmonary disease patients in community: a prospective study].

Objective: BMI may play a protective role in reducing the mortality rate of patients with chronic obstructive pulmonary disease (COPD), but its effect on acute exacerbation of COPD remain unclear. Methods: Subjects were selected from the COPD patients registration system established in 2014 in Pudong new district, Shanghai. COPD patients from 8 communities were selected by cluster sampling and follow up was conducted prospectively for 18 months. Basic information and BMI were obtained from baseline survey, and acute exacerbations were collected during follow-up. The association between BMI and risk of acute exacerbation was evaluated by using multiple negative binomial regression. Results: Among 328 community COPD patients, 295 who completed the follow up were included in the analysis, in whom 96.3% (284/295) were mild COPD patients. During the follow-up, 11.1% (33/295) of the patients reported acute exacerbation. The results of multiple negative binomial regression suggested that, the risk for acute exacerbation decreased with the increase of BMI (IRR=0.85, 95%CI:0.73-0.98), overweight patients with BMI ≥25.0 kg/m2 (IRR=0.36, 95%CI:0.13-0.91) or moderate BMI (T2 vs. T1, IRR=0.31, 95%CI:0.11-0.77) had lower risk for acute exacerbation compared with the patients with normal or low BMI. BMI had a linear correlation with the risk of acute exacerbation. Conclusion: The risk for acute exacerbation in patients with mild or moderate COPD in communities decreased with the increase of BMI, and being overweight might be a protective factor for the acute exacerbation of COPD.

Nosocomial bloodstream infection pathogen Pantoea dispersa: a case report and literature review.

Pantoea dispersa is a Gram-negative bacterium frequently found in plants, soil, and water. The genus Pantoea is a rare pathogen in human infectious diseases. The known susceptible populations include infants and postoperative and immunocompromised patients. To date, there have been no reports of nosocomial bloodstream infection due to P. dispersa following chest puncture. A 72-year-old Chinese woman suffering from chest distress was found to be blood culture positive for a Gram-negative bacterium. The organism was identified as P. dispersa through Vitek 2, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and 16S rRNA gene sequencing. Although cefoperazone-sulbactam and imipenem were used for treatment, the patient died four days later. To the best of our knowledge, this is the first case of nosocomial bloodstream infection caused by P. dispersa in China. We hope that this article might help clinicians understand better the potential pathogenicity of this pathogen.

Primary choice of estrogen and progestogen as components for HRT: a clinical pharmacological view.

Prescribing hormone replacement therapy (HRT) requires consideration of the selection of its two components, the estrogen and the progestogen. In terms of the estrogen, the decision is mainly whether to use estradiol (E2) or conjugated equine estrogens (CEE). These are the components needed to efficiently treat climacteric symptoms or/and prevent osteoporosis, currently the only labeled indications. There is still controversy regarding the adequate dosages comparing E2 and CEE; however, the consensus is that the differences in the efficacy of E2 and CEE are not a real issue. Therefore, other criteria have to be used. The first reason to add the progestogen is to avoid the development of endometrial cancer (i.e. to achieve 'endometrial safety'). Any available 'fixed-combined' HRT preparation has to be tested for sufficient endometrial efficacy, because the first question the health authorities ask before product registration relates to endometrial safety. We can generally rely on the endometrial safety of these fixed-combined products. However, it could be that we want to use 'free' combinations, which are necessary if we use transdermal E2 (patches, gel, spray), but also to individualize schedules, for example when treating bleeding problems. The question here is how to attain knowledge about the endometrial efficacy of the different progestogens and how to monitor therapy. We will try to answer these two questions from a 'clinical pharmacology' point of view, as a discipline which preferably considers pharmacological properties, but also relating to clinical practice, to achieve individualized therapy with optimal efficacy, best tolerability and minimal risks.

First live birth in China after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first live birth after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency in China. METHODS: A patient with myelodysplastic syndrome received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and six ovarian cortex strips were thawed and transplanted into her peritoneal pocket 2 years later. RESULTS: Pregnancy occurred spontaneously 27 months after grafting, and a healthy girl was born at 38 weeks gestation. Until now, the child has developed normally without any major diseases. CONCLUSIONS: We report the first live birth resulting from ovarian tissue cryopreservation and transplantation in China.

[CD36 gene deletion reduces muscle insulin sensitivity in mice by up-regulating PTP1B expression].

OBJECTIVE: To investigate the effect CD36 deficiency on muscle insulin signaling in mice fed a normal-fat diet and explore the possible mechanism. METHODS: Wild-type (WT) mice and systemic CD36 knockout (CD36-/-) mice with normal feeding for 14 weeks (n=12) were subjected to insulin tolerance test (ITT) after intraperitoneal injection with insulin (1 U/kg). Real-time PCR was used to detect the mRNA expressions of insulin receptor (IR), insulin receptor substrate 1/2 (IRS1/2) and protein tyrosine phosphatase 1B (PTP1B), and Western blotting was performed to detect the protein expressions of AKT, IR, IRS1/2 and PTP1B in the muscle tissues of the mice. Tyrosine phosphorylation of IR and IRS1 and histone acetylation of PTP1B promoter in muscle tissues were detected using co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP), respectively. RESULTS: CD36-/- mice showed significantly lowered insulin sensitivity with obviously decreased area under the insulin tolerance curve in comparison with the WT mice (P < 0.05). CD36-/- mice also had significantly higher serum insulin concentration and HOMA-IR than WT mice (P < 0.05). Western blotting showed that the p-AKT/AKT ratio in the muscle tissues was significantly decreased in CD36-/- mice as compared with the WT mice (P < 0.01). No significant differences were found in mRNA and protein levels of IR, IRS1 and IRS2 in the muscle tissues between WT and CD36-/- mice (P>0.05). In the muscle tissue of CD36-/- mice, tyrosine phosphorylation levels of IR and IRS1 were significantly decreased (P < 0.05), and the mRNA and protein levels of PTP1B (P < 0.05) and histone acetylation level of PTP1B promoters (P < 0.01) were significantly increased as compared with those in the WT mice. Intraperitoneal injection of claramine, a PTP1B inhibitor, effectively improved the impairment of insulin sensitivity in CD36-/- mice. CONCLUSION: CD36 is essential for maintaining muscle insulin sensitivity under physiological conditions, and CD36 gene deletion in mice causes impaired insulin sensitivity by up-regulating muscle PTP1B expression, which results in detyrosine phosphorylation of IR and IRS1.

E2 + norethisterone promotes the PI3K-AKT pathway via PGRMC1 to induce breast cancer cell proliferation.

OBJECTIVE: This study aimed to find evidence that progesterone receptor membrane component 1 (PGRMC1) promotes estradiol (E2) + norethisterone (NET)-induced breast cancer proliferation through activation of the phosphatidylinositol-3-kinase (PI3K)-AKT pathway. METHODS: PGRMC1-mediated breast cancer cellular proliferation and phosphorylation of PGRMC1 were studied using wild-type (hemagglutinin [HA]-tagged) MCF-7 cells, which were stably transfected with expression vector containing HA (MCF-7-HA cells), PGRMC1 (MCF-7-PGRMC1 cells) and Ser181 point mutated PGRMC1 (MCF-7-PGRMC1-S181A cells). Bioinformatics, cell proliferation, western blot, isobaric tags for relative and absolute quantitation (iTRAQ)-based RNA sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) and cell cycle in vitro assays were performed to indicate the function of PGRMC1 and its possible mechanisms in breast cancer. RESULTS: NET + E2 elicited a significant proliferation in MCF-7-Vec at 10-6 M and 10-10 M, respectively. MCF-7-PGRMC1 did increase the phosphorylation of AKT or ERK, which can be blocked by treatment with casein kinase 2 (CK2) inhibitor quinalizarin or in MCF-7-PGRMC1-S181A cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the PI3K-AKT pathway is upregulated in MCF-7-PGRMC1 cells. Importantly, upregulation of the PI3K-AKT pathway mainly through promotion of cell cycle regulation strongly promoted cell proliferation in MCF-7-PGRMC1 cells. CONCLUSIONS: CK2 is involved in phosphorylation of PGRMC1 at S181. The mechanism for the action of PGRMC1 for mediating proliferative progestogen effects obviously starts with promotion cell cycle regulation, and then activation of the PI3K-AKT pathway.

Understanding why consumers in China switch between wild, farmed and synthetic bear bile products.

An important rationale for legally-farmed and synthetic wildlife products are that they reduce illegal wild-sourced trade by supplying markets with sustainable alternatives. For this to work, more established illegal-product consumers must switch to legal alternatives than new legal-product consumers drawn to illegal wild products. Despite widespread debate on the magnitude and direction of switching, studies among actual consumers are lacking. We used an anonymous online survey of 1421 Traditional Chinese Medicine consumers in China to investigate switching between legal farmed, synthetic, and illegal wild bear bile. We examined past consumption behaviour, and applied a discrete choice experiment framed within worsening hypothetical disease scenarios, using latent class models to investigate groups with shared preferences. Bear bile consumers (86% respondents) were wealthier, more likely to have family who consumed bile, and less knowledgeable about bile treatments than non-consumers. Consumer preferences were heterogenous but most consumers preferred switching between bile types as disease worsened. We identified five distinct latent classes within our sample: 'law-abiding consumers' (34% respondents), who prefer legal products and were unlikely to switch; two 'all-natural consumer' groups (53%), who dislike synthetics but may switch between farmed and wild products; and two 'non-consumer' groups (12%) who prefer not to buy bile. People with past experience of bile consumption had different preferences than those without. Willingness to switch to wild products was related to believing they were legal, although the likelihood of switching was mediated by preferences for cheaper products sold in legal, familiar places. We show that consumers of wild bile may switch, given the availability of a range of legal alternatives, while legal-product consumers may switch to illegal products if the barriers to doing so are small. Understanding preferences that promote or impede switching should be a key consideration when attempting to predict consumer behaviour in complex wildlife markets. This article is protected by copyright. All rights reserved.

Wildlife consumer characteristics and preferences determine their likelihood and direction of switching between legal and illegal products.