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

Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.
Humans ; Medicine, Chinese Traditional/standards* ; China ; Drugs, Chinese Herbal/adverse effects* ; United States ; United States Food and Drug Administration

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

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*

Objective To observe the value of Cox proportional hazards regression model constructed based on high-resolution MRI for predicting the risk of esophageal squamous cell carcinoma(ESCC)progression after definitive chemoradiotherapy(dCRT).Methods Thirty ESCC patients who underwent dCRT were retrospectively enrolled.Quantitative and qualitative indicators of primary tumor and imaging-defined metastatic lymph nodes were analyzed based on pre-treatment high-resolution M RI.The progression-free survival(PFS)of patients were recorded.A Cox proportional hazards regression model was established to predict the risk of tumor progression based on MRI indices,and the risks of tumor progression were stratified into high and low according to the median prediction.PFS rates were compared between patients with high or low risk of tumor progression.Results Tumor thickness(HR[95％CI]=1.210[1.025,1.429],P=0.024),relationship between the tumor and aorta(HR[95％CI]=4.275[1.064,17.168],P=0.041)and lymph node signal change rate on delayed phase pre-treatment MRI(HR[95％CI]=0.049[0.007,0.362],P=0.003)were all independent factors for predicting PFS.Based on Cox proportional hazards regression model and its predicted value,PFS rate in high risk patients was lower than that in low risk patients(P＜0.05).Conclusion High-resolution MRI could be used to predict prognosis of ESCC after dCRT.

After continuous development and improvement, lung transplantation has become the preferred means to treat a variety of benign end-stage lung diseases. However, the field of lung transplantation still faces many challenges, including shortage of donor resources, preservation and maintenance of donor lungs, and postoperative complications. Lung tissue samples removed after lung transplantation are excellent clinical resources for the study of benign end-stage lung disease and perioperative complications of lung transplantation. However, at present, the collection, storage and utilization of tissue samples after lung transplantation are limited to a single study, and unified technical specifications have not been formed. Based on the construction plan of the biobank for lung transplantation in the First Affiliated Hospital of Xi'an Jiaotong University, this study reviewed the practical experience in the collection, storage and utilization of lung transplant tissue samples in the aspects of ethical review, staffing, collection process, storage method, quality control and efficient utilization, in order to provide references for lung transplant related research.

Objective:To investigate the long-term outcomes of using 3D-printed preformed titanium meshes in repair and reconstruction of orbital region.Methods:A retrospective analysis was conducted on patients with tumors invading the naso-orbito-maxillary region who underwent surgical resection and repair/reconstruction with 3D-printed preformed titanium meshes. The patients were collected at three medical centers (the Third Affiliated Hospital of Sun Yat-sen University, Xijing Hospital of Air Force Military Medical University, and Shenzhen Longgang District Ear, Nose and Throat Hospital) from 2016 to 2023. Tumor extent was evaluated radiologically, and the surgical approaches, reconstruction outcomes, surgical complications, and long-term follow-up results were analyzed.Results:A total of 46 patients from the three centers were included in this study, comprising 27 males and 19 females, with an average age of 51 years (range: from 13 to 86 years). Among them, 4 patients had benign tumors, while the remaining 42 had malignant tumors. The median follow-up duration was 60.7 months (range: from 19.0 to 75.0 months). Postoperatively, symmetrical globe position was achieved in 38 cases without significant diplopia; 4 cases exhibited enophthalmos without diplopia, and 4 cases had enophthalmos with diplopia. Twelve patients received preoperative radiotherapy, and 30 patients received postoperative radiotherapy. Six patients developed enophthalmos, and 6 experienced titanium mesh exposure after radiotherapy. Following treatment completion, 3 patients underwent repair using frontal flaps, 1 using a superficial temporal artery island flap, and 2 using free flaps. All remaining patients showed no postoperative infections, and their wounds healed normally.Conclusion:The application of 3D-printed preformed titanium mesh enables precise repair of postoperative defects in patients with naso-orbital tumors, facilitating reliable reconstruction of the orbital and facial contours with straightforward operation and dependable outcomes.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

Objective:To investigate the nutritional status of esophageal cancer patients and analyze the ability of the modified Patient-Generated Subjective Global Assessment(mPG-SGA)to evaluate nutritional status against the original PG-SGA standard.Method:We enrolled 479 patients newly diagnosed with esophageal cancer at a provincial tertiary hospital in Shenyang from August 2022 to April 2024.Blood samples were analyzed for nutritional indicators,and nutritional status was assessed using both PG-SGA and mPG-SGA.The nutritional assessment ability of mPG-SGA was evaluated using specificity,sensitivity,area under the curve(AUC),weighted kappa coefficient,and correlation analysis.Results:Among the 479 patients,the incidence of moderate-to-severe malnutrition was 74.9%(by PG-SGA)and 72.9%(by mPG-SGA).Using PG-SGA as the standard,mPG-SGA demonstrated sensitivities of 95.4%,100%,and 100%;specificities of 98.5%,92.3%,and 89.5%;and AUC values of 0.997,0.994,and 0.989(all P<0.001)for distinguishing mild vs.moderate-to-severe malnutrition,mild-to-moderate malnutrition,and moderate-to-severe malnutrition,respectively.The overall weighted Kappa coefficient between the scales was 0.898(P<0.001).Conclusion:Malnutrition is highly prevalent among esophageal cancer patients.The mPG-SGA shows strong accuracy and consistency with PG-SGA in assessing nutritional status.Given its simplicity and efficiency,mPG-SGA may become a primary nutritional assessment tool for this population,though further multicenter validation with larger samples is warranted.

Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.