Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

Objective : To construct a human keratinocyte-forming cell line(HaCaT) with stable knockout of the G protein-coupled receptor 107(GPR107) gene, and to preliminarily investigate the effect of GPR107 deletion on the biological behaviour of HaCaT cells. Methods : Using CRISPR/Cas9 gene editing technology, HaCaT cells with knockout ofGPR107gene were constructed and monoclonal cells with GPR107 deletion were obtained by limited dilution method. Genomic DNA was amplified using Western blot and PCR and sequenced to validate the single-cell clones with knockdown of GPR107. The cell cycle changes were detected by flow cytometry; cell proliferation was detected by CCK-8; apoptosis was detected by flow cytometry; changes in cell differentiation markers were detected by Western blot; cell migration ability was analyzed by cell scratch assay and other methods. Results : LentiCas9-Blast and plenti-guide-RNA-GPR107 plasmids were successfully transfected into HaCaT cells, 21 monoclonal cell lines were obtained by limited dilution, and Western blot showed that the GPR107 expression was significantly reduced in 8 of them; PCR sequencing of the cellular genome was used, which resulted in the obtainment of C4 and 2D8GPR107-/-HaCaT monoclonal cell lines. CCK-8 assay and flow cytometry assay showed thatGPR107gene deletion resulted in G0G1phase block, significantly weakened proliferation ability and increased apoptosis level of HaCaT cells. Western blot found that the differentiation of HaCaT cells accelerated after knockdown ofGPR107. Additionally the results of the cell scratch assay indicated that the migration ability of HaCaT cells was enhanced after knockdown ofGPR107. The results showed that the migration ability of HaCaT cells was enhanced after knockdown ofGPR107. Conclusion HaCaT cell line withGPR107gene deletion is successfully constructed, GPR107 deletion blocks the G0G1phase of HaCaT cells, which inhibiting the proliferation of HaCaT cells and promoted apoptosis, and it was found that the differentiation and migration of HaCaT cells were enhanced after knocking downGPR107.

Objective:To analyze the willingness and related factors of pregnant women in Shanghai City to receive influenza vaccines during pregnancy.Methods:An online questionnaire survey was conducted among pregnant women who registered in maternal and child health hospitals in 16 districts of Shanghai. The basic information, health status during pregnancy, attitude towards influenza vaccination, and knowledge of influenza and influenza vaccine were collected, and χ2 test and multivariate logistic regression analysis were used to analyze the willingness and related factors of pregnant women to receive influenza vaccines during pregnancy. Results:A total of 3 219 valid questionnaires were received, with 10.90% of pregnant women willing to receive influenza vaccination during pregnancy, 57.50% unwilling to receive vaccination and 31.59% holding an uncertain attitude. Among the pregnant women who were willing to receive the vaccine, 82.91% would take the initiative to know the relevant information about the influenza vaccine, and 87.18% understood the transmission routes of the flu. 32.09% believed that pregnant women could receive the influenza vaccination at any stage of pregnancy. Among those who were unwilling and held an uncertain attitude, the proportions of the above three questions were 47.06%, 83.95% and 17.80%, respectively. Among pregnant women who were unwilling to receive vaccination and held an uncertain attitude, the main reason for their vaccine hesitation was the concern about the safety of the vaccine for pregnant women and fetuses during pregnancy. Multivariate logistic regression analysis showed that pregnant women with higher education ( OR=3.278, 95% CI: 1.678-6.406, P=0.001), second trimester ( OR=1.542, 95% CI: 1.159-2.054, P=0.003), third pregnancy ( OR=2.318, 95% CI: 1.008-5.331, P=0.048), and previous influenza vaccination ( OR=1.552, 95% CI: 1.119-2.152, P=0.008) had a higher willingness to receive influenza vaccines during pregnancy. Conclusion:Pregnant women in Shanghai have a relatively low willingness to receive influenza vaccines during pregnancy, mainly due to concerns about vaccine safety.

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of dehydrodiisoeugenol,eugenol,costiolactone,dehydrocostiolactone,quercetin,isorhamnetin,luteolin,caffeic acid,gallic acid,protocatechuic acid,ellagic acid and kaempferol in Anshen Buxin Liuwei Pills,and to make chemical pattern recognition.METHODS The analysis was performed on a 35 ℃ thermostatic Shim-pack GST-HP C18 column(2.1 mm × 100 mm,3 μm),with the mobile phase comprising of methanol-water(containing 0.1％formic acid)flowing at 0.25 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.Subsequently,cluster analysis,principal component analysis and orthogonal partial least square-discriminant analysis were performed.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 95.38％-105.00％with the RSDs of 1.91％-5.14％.Thirteen batches of samples were clustered into 3 types,ellagic acid,dehydrocodenolactone,dehydrodiisoeugenol,protocatechuic acid,gallic acid,quercetin and kaempferol were taken as potential quality differential markers.CONCLUSION This accurate,sensitive,stable and reproducible method can be used for the quality control and evaluation of Anshen Buxin Liuwei Pills.

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

Randomized controlled trial(RCT) is considered to represent the gold standard for evaluating the efficacy of interventions and has been widely used to evaluate the clinical efficacy of traditional Chinese medicine(TCM). However, there are unique challenges in implementing RCT in TCM. Patients seeking TCM treatment often have preferences for TCM due to the unsatisfactory therapeutic effect of western medicine, their personal intolerance, and their rejection of certain drugs, medical devices, or surgery. Patients are generally reluctant to be randomly assigned to a group, making it challenging to enroll patients in the control group of western medicine during the implementation of RCT in TCM. This has become a prominent problem restricting the implementation of RCT in TCM and needs to be solved urgently. Therefore, this paper introduced commonly used research designs used in solving the problem of enrolling patients in control group during the implementation of RCT in TCM, including Zelen design, partially randomized patient preference trial(PRPP), single-arm objective performance criteria(OPC), cohort studies, single-arm clinical trials using real world data(RWD) alone as the external control group, and the design method based on RWD-augmented control group samples in RCT. The paper outlined the definitions and principles of these methods, evaluated their advantages, disadvantages, and applicable scenarios, and explored their applications in the TCM field, so as to offer insights for solving the difficulty in enrolling patients in the control group during the implementation of RCT in TCM.
Humans ; Medicine, Chinese Traditional/methods* ; Randomized Controlled Trials as Topic/methods* ; Research Design ; Patient Selection ; Drugs, Chinese Herbal/therapeutic use* ; Control Groups

Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout