Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To construct a prediction model for postoperative healthcare-associated infection(HAI)in elderly patients with hip fracture,analyze the economic burden,provide a reference and basis for the development of clinical prevention and control programs.Methods 627 elderly patients who underwent hip fracture surgery in a hospital from January 1,2017 to May 31,2023 were selected as the study subjects.Patients were randomly divided into a modeling group and a validation group at a 7:3 ratio.A logistic regression prediction model was constructed based on data from the modeling group,the discriminant and consistency of the model were evaluated by receiver ope-rating characteristic(ROC)curve and Hosmer-Lemeshow test,and the direct economic burden of postoperative HAI in patients was analyzed with 1∶1 propensity score matching(PSM).Results The incidence of postoperative HAI in elderly patients with hip fracture surgery was 12.1％,with pulmonary infection being the most common(52.6％).Logistic regression analysis showed that male,old age,perioperative disturbance of consciousness,gradeⅣ of American Society of Anesthesiologists(ASA)classification,low albumin level,and intensive care unit(ICU)admission were all independent risk factors for postoperative HAI in patients(all P＜0.05).There was good model discrimination and consistency between the training and validation groups in predicting the risk of postoperative HAI.The direct economic burden of postoperative HAI in patients was 7 927.4 Yuan,of which the burden of wes-tern medicine was the largest(3 139.7 Yuan).HAI prolonged patients hospitalization time by 3.6 days.Conclusion Postoperative HAI increases the economic burden of patients,the nomogram model constructed in this study can effectively predict the risk of postoperative HAI in patients,which can provide a basis for the early identification,as well as the implementation of targeted preventive and diagnostic measures for high-risk patients in the clinic.

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.
Female ; Humans ; Moxibustion ; Meridians ; Acupuncture Points ; Acupuncture Therapy ; Foot ; Genital Diseases, Female/therapy*

BACKGROUND: Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19. OBJECTIVE: To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis. METHODS: A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group. RESULTS: Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05). CONCLUSIONS LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).
COVID-19/drug therapy* ; Cough/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Dyspnea/drug therapy* ; Fatigue/drug therapy* ; Humans ; Myalgia/drug therapy*

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Zexietang is a Chinese herbal compound prescription with a long history， which consists of Rhizoma alismatis and Atractylodes macrocephala. Zexietang comes from "Synopsis of Golden Chamber"， as "there is a drink under the heart， and its people are bitter and dizzy". Zexietang has the effect of removing water from drinking water and invigorating spleen for diuresis. Modern pharmacological studies have shown that its lipid-lowering and anti-inflammatory effects are very significant. It can be used to treat hyperlipidemia， anti-atherosclerosis and non-alcoholic fatty liver disease. With the continuous development of molecular biology， the research on the pharmacological effects of Zexietang， extracts and their monomers has deepened to the molecular level gradually， and the relevant mechanism of action has also been continuously elucidated. In terms of lipid-lowering effect of Zexietang， the levels of cytokines or receptors such as 3-hydroxy-3-methyl glutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， and liver X receptors （LXR） are affected. It is widely involved in adenosine 5'-monophosphate-activated protein kinase （AMPK） and peroxisome proliferators-activated receptors （PPAR） pathways， while Zexietang's anti-inflammatory effect mainly affects inflammatory factors such as interleukins （IL） and tumor necrosis factors （TNF）， and simultaneously nuclear factor κB （NF-κB）， toll-like receptors （TLR） and other cytokines or receptor-related pathways. In order to promote the further research and clinical application of Zexietang and contribute to the development of modernization of traditional Chinese medicine， the studies of the past 15 years on molecular mechanism of the lipid-lowering and anti-inflammatory effect of Zexietang， Alisma and Atractylodes extract as well as their monomer components were reviewed.

Objective:To establish a high performance liquid chromatography （HPLC） fingerprint of branches of Juglans mandshurica and to evaluate the quality of the samples from different producing areas and in different harvest periods. Method:Chromatographic separation was performed on an Agilent Poroshell 120 SB-C₁₈ column （2.1 mm×100 mm， 2.7 μm） for gradient elution with mobile phase of 0.2% formic acid solution （A）-0.2% formic acid acetonitrile solution （B） （0-5 min， 5%-10%B； 5-25 min， 10%-16%B； 25-40 min， 16%-22%B； 40-45 min， 22%-45%B； 45-50 min， 45%-65%B； 50-52 min， 65%-100%B； 52-55 min， 100%B） at a flow rate of 0.3 mL·min^-1. The column temperature was 30 ℃ and the detection wavelength was 270 nm. The quality of branches of Juylans mandshurica was evaluated by similarity evaluation， cluster analysis， principal component analysis and partial least squares-discriminant analysis. The chemical constituents of the samples were identified by HPLC coupled with quadrupole time-of-flight mass spectrometry （HPLC-Q-TOF-MS/MS）. The mass spectrometry was conducted in negative ion mode with electrospray ionization（ESI）. Data were acquired over a range of m/z 100-1 700 for MS and m/z 50-1 700 for MS/MS. Result:A total of 19 common peaks were confirmed in 40 batches of samples， and the similarity ranged from 0.430 to 0.995， of which the similarity of samples collected in spring and winter seasons （April， May and December） was greater than 0.90， while the similarity of most samples collected in summer （July to September） was low. Multivariate statistical analysis showed that the samples were divided into two groups according to the harvest time， but there was no obvious classification rule for the samples from different producing areas. The contents of most constituents in the samples collected in spring and winter were higher than those collected in summer. The result illustrated that different harvest periods had great influence on the quality of branches of J. mandshurica. Compared with the samples collected in summer， the quality of samples collected in spring and winter was better. A total of 22 peaks were proved to be the main constituents that contributed to the difference between samples collected in different seasons. A total of 83 chemical components were identified by HPLC-Q-TOF-MS/MS， including 49 tannins， 7 organic acids， 14 naphthalene derivatives， 1 flavonoid， 6 anthracene derivatives， 2 lignans， 3 diarylheptanoids and 1 saccharide. Totally 13 common peaks were identified. Of the peaks that contributed to discriminate samples collected in different season， 19 peaks were identified and most of them were tannins. Conclusion:The established HPLC fingerprint can provide useful information for the quality evaluation of branches of J. mandshurica. Tannin is the main constituents in the samples. Harvest period has great influence on the quality of branches of J. mandshurica.

Objective: To explore the relationship between sleep problems and non-suicidal self-injury behavior in Chinese college students, and to provide scientific basis for the prevention and intervention of non-suicidal self-injury behavior. Methods: A cross-sectional survey of 11 689 college students from three universities in Guangzhou were selected as the research subjects. A questionnaire survey of college students’ mental health was conducted to investigate non-suicidal self-injury behavior, sleep problems, demographic information, lifestyle, and depressive symptoms. Results: In the past year, the prevalence rates of non-suicidal self-injury in college students was 7.8%. Univariate Logistic analysis showed that all sleep problems were associated with non-suicidal self-injury behavior(P<0.05). After controlling for potential confounders,including grade,gender,parents’ education level,health conditon,family income,smoking,drinking and depression,multivariate Logistic regression showed that shorter sleep time at weekend (<7 h/d), insomnia symptoms and frequent nightmares significantly increased the risk of nonsuicidal selfinjury behavior in college students (OR=1.32-3.25, P<0.05), while longer sleep time at weekdays (≥9 h/d) was an important protective factor (OR=0.60, P<0.05). Conclusion These findings indicate that short sleep time, insomnia and nightmares are important risk factors for college students’ non-suicidal self-injury behavior. Intervention and management on sleep problems can effectively reduce the occurrence of self-injury behaviors.