Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

In China， the incidence of ischemic heart disease （IHD） is increasing year by year， which brings enormous burden to families and society. It is urgent to find preferable treatment methods and medical therapies. The Chinese ethnic minority medicine has gradually developed unique theoretical systems and therapeutic characteristics on the basis of clinical experience and thinking modes including image-number thinking and the holistic perspective. Consequently， it possesses huge application capacity and research value in prevention and treatment of IHD. Belonging to the medical system based on the view of nature and life， the Tibetan medicine， Mongolian medicine， and Dai medicine have respectively formed theories like "three elements" "three life-sustaining energies" "four elements and five skandhas （aggregates）" ， have put forward unique understandings of IHD and have formed corresponding therapeutic principles and methods， generating plentiful classic prescriptions represented by Sanwei Tanxiang powder， Bawei Chenxiang powder， Roukou Wuwei pills and Yajiao Hadun powder. They also contain characteristic ethnic medicine resources such as Choerospondiatis Fructus， Rhodiola Rosea and Draconis Sanguis. Aiming to provide enlightenment and reference for the clinical application and development of the Chinese ethnic minority medicine for the prevention and treatment of IHD， the authors try to summarize the related researches represented by Tibetan and Mongolian medicines， and then discuss the opportunities and challenges faced by such researches.

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

OBJECTIVETo investigate the therapeutic effect of facial artery perforator flap for the soft tissue defects at nose, lip and cheek.

METHODSThe facial artery perforator adjacent to the defect was identified by Doppler ultrasonography. The perforator flap was designed according to the defect location, size and shape. The subcutaneous tissue around the perforator was kept as much as possible to protect the venous drainage.

RESULTSFrom Oct. 2012 to Oct.2013, 26 cases were treated with facial artery perforator flaps, with 9 cases of nasal defects, 10 cases of lip defects and 7 cases of buccal defects. The defects size ranged from 1.5 cm x 2.0 cm to 3.0 cm x 3.0 cm and the flaps size ranged from 2.0 cm x 2.5 cm to 3.5 cm x 3. 5 cm. Superficial necrosis(3mm in width) happened at the end of one flap. All the other 25 flaps survived completely. 16 cases were followed up for 3 months to 2 years with no relapse and satisfactory cosmetic and functional results were achieved.

CONCLUSIONSBoth cosmetic and functional effect can be achieved with facial artery perforator flap for defects at nose, lip and cheek.

Arteries ; Cheek ; surgery ; Graft Survival ; Humans ; Lip ; surgery ; Nose ; surgery ; Perforator Flap ; blood supply ; transplantation ; Rhinoplasty ; methods

Objective To explore the effect of pharyngeal chili sauce and cold stimulation on swallowing function of patients with stroke coma.Methods A total of 93 patients with stroke coma were included and randomly divided into three groups.The oral nursing and glossopharyngeal massage were performed in control group (n =30).The oral nursing and cold stimulation were performed in cold stimulation group (n =32).The oral nursing and chili sauce stimulation were performed in chili sauce stimulation group (n =31).The swallowing movement,duration of tracheotomy and incidence of stroke-associated pneumonia were compared among three groups.Results Ten minutes after oral nursing,the swallowing frequency in control group,cold stimulation group and chili sauce stimulation group was (21.09 ±9.16),(34.16 ±20.43)and (49.31 ±25.17), respectively.The difference was statistically significant (F =12.962,P <0.05).The duration of tracheotomy in control group,cold stimulation group and chili sauce stimulation group was (37.60 ±13.42)d,(29.19 ±8.24)d and (22.04 ±8.23)d,respectively.The difference was statistically significant (F =12.639,P <0.05).The incidence of stroke-associated pneumonia in three groups was 43.33%,37.50% and 35.48%,respectively. there was no significant difference among three groups (χ2 =0.616,P >0.05).Conclusions Both pharyngeal chili sauce and cold stimulation can improve swallowing function of patients with stroke coma.The pharyngeal chili sauce stimulation can stimulate swallowing movement for a longer time to help the recovery of swallowing function,and can shorten the duration of tracheotomy.

OBJECTIVESince 1986, the reference of birth weight for gestational age has not been updated. The aim of this study was to set up Chinese neonatal network to investigate the current situation of birth weight in China, especially preterm birth weight, to develop the new reference for birth weight for gestational age and birth weight curve.

METHODA nationwide neonatology network was established in China. This survey was carried out in 63 hospitals of 23 provinces, municipalities and autonomous regions. We continuously collected the information of live births in participating hospitals during the study period of 2011-2014. Data describing birth weight and gestational age were collected prospectively. Newborn's birth weight was measured by electronic scale within 2 hours after birth when baby was undressed. The evaluation of gestational age was based on the combination of mother's last menstrual period, ultrasound in first trimester and gestational age estimation by gestational age scoring system.

STATISTICAL ANALYSISthe growth curve was drawn by using LMSP method, which was conducted in GAMLSS 1.9-4 software package in R software 2.11.1.

RESULTA total of 159 334 newborn infants were enrolled in this study. There were 84 447 male and 74 907 female. The mean birth weight was (3 232 ± 555) g, the mean birth weight of male newborn was (3 271 ± 576) g, the mean weight of female newborn was (3 188 ± 528) g. The test of the variables' distribution suggested that the distribution of gestational age and birth weight did not fit the normal distribution, the optimal distribution for them was BCT distribution. The Q-Q plot test and worm plot test suggested that this curve fitted the distribution optimally. The male and female neonatal birth weight curve was developed using the same method.

CONCLUSIONUsing GAMLSS method to establish nationwide neonatal birth weight curve, and the first time to update the birth weight reference in recent 28 years.

Birth Weight ; China ; Female ; Gestational Age ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Male

OBJECTIVETo explore the relationship between job burnout and cognitive function and the influencing factors of job burnout among medical staff.

METHODSQuestionnaire survey was conducted for 197 medical workers in a grade-three general hospital in Beijing. Maslach Burnout Inventory-General Survey (MBI-GS) was carried out to assess the degree of job burnout among medical staff; Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to evaluate the overall cognitive function and cognitive situations of different dimensions.

RESULTS(1) There was a certain level of job burnout among medical staff, especially for the emotional exhaustion dimension (13.29 ± 7.67). (2) High level job burnout group (81.08 ± 12.34) scored lower on visual span than low level job burnout group (92.48 ± 19.62), P<0.05. Overall, job burnout had a negative influence on the general cognitive function (P<0.05). (3) The results of regression analysis indicated that, inefficacy was negatively correlated with age (r=-0.162, P<0.05). Job burnout was positively correlated with level of education (r=0.234, P<0.05) as well as exercise frequency (r=0.320, P< 0.001), and emotional exhaustion was correlated with overtime work (r=0.135, P<0.05); Level of job burnout stayed higher among doctors and nurses, compared with administration staff in hospitals (t=2.966, P<0.05).

CONCLUSIONJob burnout of medical staff was relatively in high level; influenced by age, education level, overtime work, exercise frequency and occupational type, job burnout affected the visual span and general cognitive function.

Burnout, Professional ; Cognition ; Hospitals ; Humans ; Medical Staff ; psychology ; Nurses ; supply & distribution ; Physicians ; psychology ; Regression Analysis ; Surveys and Questionnaires

Objective To explore the effects of a single bout of aerobic exercise on oxidative stress and total peripheral vascular resistance. Methods 36 prehypertensive patients were divided into aerobic exercise group (n=18) and control group (n=18). The aerobic exercise group performed cycle ergometry at 70% maximal oxygen consumption for 30 min. Total peripheral vascular resistance (TPVR), malondialdehyde (MDA), mean arterial pressure (MAP), vitamin C (VC) and vitamin E (VE) were measured before, immediately, 1 hour and 2 hours after the aerobic exercise. Results There was no significant difference in TPVR, MDA, MAP, VC and VE between two groups before exercise (P>0.05). TPVR was all significantly lower in the aerobic exercise group than in the control group immediately, 1 hour and 2 hours after exercise (P<0.001), and showed a rising trend of recovery. MDA was significantly higher in the aerobic exercise group than in the control group 1 hour and 2 hours after exercise (P<0.05), however there was no significant difference in MDA between two groups immediately after exercise (P>0.05). MAP was significantly lower immediately after exercise in the aerobic exercise group than in the control group (P< 0.001), but there was no significant 1 hour and 2 hours after exercise (P>0.05). There was no significant difference in VC and VE between two groups immediately, 1 hour and 2 hours after exercise (P>0.05). Conclusion The level of oxidative stress increases after a single bout of aerobic exercise, and the TPVR decreases.

From the visual angle of mechanics, bone remodelling plays an important role in adapting to load environment and repairing microcracks. In order to describe the process of bone remodelling explicitly, we introduced a bone remodelling model representing the biological features of damage/repair in bone. Based on Basic Multicellular Units (BMUs), the model embodies not only the mechano-transduction of osteocytes' response to mechanical stimuli, but also the biological process of the randomly ocurring microcracks that are resorbed by osteoclasts and then refilled by osteoblasts. A 2-D trabecular bone finite element model was used as an initial configuration in the research. The developments in bone microstructure and material properties have been monitored in the course of 10 simulated years. The conclusions are: (1) Initially, trabecular bone changes prominently, but it tends to be stable later on; (2) The material properties of trabecular bone in compression are much better than in tension.
Biomechanical Phenomena ; Bone Remodeling ; physiology ; Bone and Bones ; injuries ; pathology ; physiology ; Humans ; Models, Biological ; Stress, Mechanical ; Wound Healing