Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Ganjiang (Zingiberis Rhizoma, ZR) and Jiangtan (Carbonized Zingiberis Rhizoma, CZR) have long been used in traditional Chinese medicine (TCM) with a rich history in the treatment of various ailments. While ZR and CZR obviously stem from the same botanical source, their attributes, chemical compositions, pharmacological behaviors, and clinical applications are different owing to variations in the extent of drying and processing they undergo. In this paper, data pertaining to ZR and CZR were retrieved from databases including China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and Google Scholar. These sources were scrutinized to elucidate the distinctions between ZR and CZR arising from carbonization processing in terms of their ethnopharmacology, quality control, chemical compositions, biological activities, pharmacological mechanisms, and clinical uses. In this study, a total of 56 chemical constituents were identified and isolated from ZR and CZR, which primarily encompassed volatile oils, gingerols, and diphenylheptane compounds. CZR's pharmacological effects include hemostatic, anti-oxidant, analgesic, antibacterial, anti-cancer, and other biological activities. ZR has pungent and warm properties. It is a Yang-supplementing herbal medicine for ailments exacerbated by cold or damp climatic influences. CZR is a product of ZR after undergoing high temperature, with diminished intensity of its pungent and warm attributes. This change leads to a more gradual treatment efficacy, renowned hemostatic effects and its ability to gently invigorate the spleen and effectively alleviate diarrhea. Currently, research on the pharmacological mechanism of CZR is mainly focused on the effects of CZR on coagulation and fibrinolysis. Although the healing effect of CZR has long been known, and some correlation has been found between the changing composition and the changing color of the decoctions, people still lack relatively clear processing mechanisms to reflect the characteristics and specific quality standards of the ingredients of CZR's hemostatic effect. This review provides a systematic summary on quality control, chemical composition, ethnopharmacology, and pharmacology of CZR, offering novel perspectives for advancing the exploration of additional carbonized herbal medicine and fostering their application in clinical settings

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END⁺/Gal⁺-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

Objective:To analyze the relationship between arch index and foot kinematic parameters and their characteristics in stress fracture of lower extremity.Methods:A case-control study was performed for 108 recruits selected from a certain army unit in 2019. Before training, the recruits′ foot print images were collected by the capacitive plantar pressure measurement system to calculate their arch indices. The kinematic characteristics of the foot were analyzed by the dynamic gait posture analysis system. Spearman rank correlation analysis between arch index and foot kinematic parameters including landing elevation angle, toe-off angle, landing speed, landing varus angle, valgus amplitude and landing valgus speed were performed. Throughout the training, orthopedic physicians followed up the recruits, among whom 10 were excluded due to other types of lower extremity injuries. The arch index and foot kinematic characteristics were analyzed and compared between the remained recruits with stress fracture of lower extremity (fracture group, n=10) and those without lower extremity injury (control group, n=79). Results:(1) For the recruits, the arch index was 0.21(0.12,0.25), with landing elevation angle for (17.31±4.02)°, toe-off angle for (63.90±5.63)°, landing speed for (176.85±24.39)°/s, landing varus angle for (13.64±4.44)°, valgus amplitude for (12.16±3.42)°, and landing valgus speed for 382.50(311.05,474.80)°/s. (2) The landing varus angle ( r=0.25, P<0.01) and valgus amplitude ( r=0.14, P<0.05) were positively related to the arch index. (3) The arch index, toe-off angle and landing valgus speed were 0.20(0.07,0.24), (61.59±5.51)° and 336.00(251.02,428.67)°/s in fracture group, significantly lower than 0.23(0.17,0.26), (64.79±4.79)° and 381.20(313.63,470.92)°/s in control group ( P<0.05 or 0.01). There were no significant differences in the landing elevation angle, landing speed, landing varus angle and valgus amplitude between the two groups (all P>0.05). Conclusions:The change of the arch index can affect the landing varus angle and valgus amplitude of the foot. Recruits who suffer from stress fracture of lower extremity have the characteristics of higher arch, lower toe-off angle and lower landing valgus speed.

Objective:To investigate the possible functional roles and mechanisms of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, reactive oxygen species (ROS), and aldo-keto reductase family 1 member C3 (AKR1C3) in keloid formation.Methods:Nine keloid tissues from patients (six males, three females; aged: 24-40 years old) and six normal skin tissues from healthy controls (four males, two females; aged 24-45 years old) were collected. Tissue samples were embedded or used in fibroblasts isolation and culture. (1) The relative expression of protein kinase B serine phosphorylation site 473[p-AKT (S473)], protein kinase B threonine phosphorylation site 308[p-AKT (T308)], and AKR1C3 in keloid tissues and normal skin tissues was measured using immunohistochemistry. (2) The CCK-8 assay was employed to detect the inhibitory effect of PI3K-specific inhibitor LY294002 (0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 mmol/L) on the proliferation of keloid fibroblasts and to screen the optimal experimental concentration of LY294002. (3) The ROS assay kit was used to detect the effects of different concentrations (0, 4, 6, 8, 10, 12 mmol/L) of the ROS inhibitor N-acetylcysteine (NAC) and 15 mmol/L LY294002 on ROS levels in keloid fibroblasts. (4) Fibroblasts derived from keloid tissues or normal skin tissues were divided into control group (without any treatment), respectively, dimethyl sulfoxide(DMSO) group (0.002% DMSO treatment), LY294002 group (15 mmol/L LY294002 treatment), and NAC group (6 mmol/L NAC treatment), respectively. Quantitative PCR (qPCR) and Western blotting assays were performed to detect the levels of AKT mRNA, AKR1C3 mRNA and the protein levels of p-AKT(S473), p-AKT(T308), and AKR1C3. Statistical analysis was performed with SPSS 22.0. Data was presented as Mean±SD. Independent sample t-test was used for comparison between two groups, one-way ANOVA was used for comparison between multiple groups, and SNK- q test was used for multiple comparisons between two groups. Results:(1) Immunohistochemistry showed that the expression levels of p-AKT(S473), p-AKT(T308), and AKR1C3 in keloid tissues were 16.75±3.30, 16.20±1.56, 26.69±2.50, which were significantly higher than those in normal skin tissues: 4.02±1.50, 1.82±0.50, 1.47±1.07 ( P<0.01). (2) The proliferation inhibition rate of keloid fibroblasts treated by different concentrations of LY294002 (15-50 mmol/L LY294002) for 24 h was significantly higher than in the control group (0 mmol/L) ( P<0.01). The optimal experimental concentration of LY294002 is 15 mmol/L. (3) After different concentrations of NAC were applied to keloid fibroblasts for 1 h, the differences in ROS level was groups were statistically significant ( P<0.01), and the lowest ROS level was found in the 6 mmol/L NAC group(0.72±0.03). The 15 mmol/L LY294002 group had significantly lower ROS levels than the control group (0 mmol/L) (0.80±0.01 vs. 0.86±0.01, P<0.01). (4) qPCR showed that the mRNA levels of AKT and AKR1C3 were 1.38±0.09 and 1.40±0.05 in keloid fibroblasts in control group, which were significantly higher than those in normal skin fibroblasts: 0.97±0.10, 0.98±0.03( P<0.01). The expression level of AKT mRNA in keloid fibroblasts treated with 15 mmol/L LY294002 was significantly lower than that in normal skin fibroblasts (0.73±0.05 vs. 0.89±0.06, P<0.01). The expression level of AKR1C3 mRNA in keloid fibroblasts treated with 6 mmol/L NAC was significantly lower than that in normal skin fibroblasts (0.43±0.05 vs. 0.86±0.03, P<0.01). Western blotting revealed the expression levels of p-AKT(S473), p-AKT(T308), and AKR1C3 in keloid fibroblasts were 1.19±0.21, 0.92±0.04, 0.73±0.08, significantly higher than those in normal skin fibroblasts (0.24±0.06, 0.33±0.05, 0.31±0.05, P<0.01). After treatment with 15 mmol/L LY294002 or 6 mmol/L NAC, the protein expression of p-AKT (S473) in keloid fibroblasts were 0.92±0.04 and 0.80±0.20; the protein levels of p-AKT (T308) were 0.42±0.04 and 0.81±0.05, which were all significantly higher than the expression levels in normal skin tissue (0.23±0.03, 0.22±0.05, 0.30±0.06, 0.32±0.05). However, The expression of AKR1C3 protein in keloid fibroblasts treated with 15 mmol/L LY294002 (0.23±0.05) was significantly lower than that in normal skin fibroblasts (0.30±0.07), the expression of AKR1C3 protein in keloid fibroblasts treated with 6 mmol/L NAC (0.33±0.07) was significantly higher than that in normal skin fibroblasts (0.28±0.06, P>0.05). Conclusions:Activation of PI3K/AKT signaling pathway and AKR1C3 promoted the proliferation of keloid fibroblasts and keloid formation. Meanwhile, the elevation of AKR1C3 accelerated the increase of ROS level in keloid fibroblasts.

Objective:To investigate the possible functional roles and mechanisms of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, reactive oxygen species (ROS), and aldo-keto reductase family 1 member C3 (AKR1C3) in keloid formation.Methods:Nine keloid tissues from patients (six males, three females; aged: 24-40 years old) and six normal skin tissues from healthy controls (four males, two females; aged 24-45 years old) were collected. Tissue samples were embedded or used in fibroblasts isolation and culture. (1) The relative expression of protein kinase B serine phosphorylation site 473[p-AKT (S473)], protein kinase B threonine phosphorylation site 308[p-AKT (T308)], and AKR1C3 in keloid tissues and normal skin tissues was measured using immunohistochemistry. (2) The CCK-8 assay was employed to detect the inhibitory effect of PI3K-specific inhibitor LY294002 (0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 mmol/L) on the proliferation of keloid fibroblasts and to screen the optimal experimental concentration of LY294002. (3) The ROS assay kit was used to detect the effects of different concentrations (0, 4, 6, 8, 10, 12 mmol/L) of the ROS inhibitor N-acetylcysteine (NAC) and 15 mmol/L LY294002 on ROS levels in keloid fibroblasts. (4) Fibroblasts derived from keloid tissues or normal skin tissues were divided into control group (without any treatment), respectively, dimethyl sulfoxide(DMSO) group (0.002% DMSO treatment), LY294002 group (15 mmol/L LY294002 treatment), and NAC group (6 mmol/L NAC treatment), respectively. Quantitative PCR (qPCR) and Western blotting assays were performed to detect the levels of AKT mRNA, AKR1C3 mRNA and the protein levels of p-AKT(S473), p-AKT(T308), and AKR1C3. Statistical analysis was performed with SPSS 22.0. Data was presented as Mean±SD. Independent sample t-test was used for comparison between two groups, one-way ANOVA was used for comparison between multiple groups, and SNK- q test was used for multiple comparisons between two groups. Results:(1) Immunohistochemistry showed that the expression levels of p-AKT(S473), p-AKT(T308), and AKR1C3 in keloid tissues were 16.75±3.30, 16.20±1.56, 26.69±2.50, which were significantly higher than those in normal skin tissues: 4.02±1.50, 1.82±0.50, 1.47±1.07 ( P<0.01). (2) The proliferation inhibition rate of keloid fibroblasts treated by different concentrations of LY294002 (15-50 mmol/L LY294002) for 24 h was significantly higher than in the control group (0 mmol/L) ( P<0.01). The optimal experimental concentration of LY294002 is 15 mmol/L. (3) After different concentrations of NAC were applied to keloid fibroblasts for 1 h, the differences in ROS level was groups were statistically significant ( P<0.01), and the lowest ROS level was found in the 6 mmol/L NAC group(0.72±0.03). The 15 mmol/L LY294002 group had significantly lower ROS levels than the control group (0 mmol/L) (0.80±0.01 vs. 0.86±0.01, P<0.01). (4) qPCR showed that the mRNA levels of AKT and AKR1C3 were 1.38±0.09 and 1.40±0.05 in keloid fibroblasts in control group, which were significantly higher than those in normal skin fibroblasts: 0.97±0.10, 0.98±0.03( P<0.01). The expression level of AKT mRNA in keloid fibroblasts treated with 15 mmol/L LY294002 was significantly lower than that in normal skin fibroblasts (0.73±0.05 vs. 0.89±0.06, P<0.01). The expression level of AKR1C3 mRNA in keloid fibroblasts treated with 6 mmol/L NAC was significantly lower than that in normal skin fibroblasts (0.43±0.05 vs. 0.86±0.03, P<0.01). Western blotting revealed the expression levels of p-AKT(S473), p-AKT(T308), and AKR1C3 in keloid fibroblasts were 1.19±0.21, 0.92±0.04, 0.73±0.08, significantly higher than those in normal skin fibroblasts (0.24±0.06, 0.33±0.05, 0.31±0.05, P<0.01). After treatment with 15 mmol/L LY294002 or 6 mmol/L NAC, the protein expression of p-AKT (S473) in keloid fibroblasts were 0.92±0.04 and 0.80±0.20; the protein levels of p-AKT (T308) were 0.42±0.04 and 0.81±0.05, which were all significantly higher than the expression levels in normal skin tissue (0.23±0.03, 0.22±0.05, 0.30±0.06, 0.32±0.05). However, The expression of AKR1C3 protein in keloid fibroblasts treated with 15 mmol/L LY294002 (0.23±0.05) was significantly lower than that in normal skin fibroblasts (0.30±0.07), the expression of AKR1C3 protein in keloid fibroblasts treated with 6 mmol/L NAC (0.33±0.07) was significantly higher than that in normal skin fibroblasts (0.28±0.06, P>0.05). Conclusions:Activation of PI3K/AKT signaling pathway and AKR1C3 promoted the proliferation of keloid fibroblasts and keloid formation. Meanwhile, the elevation of AKR1C3 accelerated the increase of ROS level in keloid fibroblasts.

Objective:To investigate the correlation between variations in mitochondrial DNA (mtDNA) control region (D-loop) and keloids.Methods:A total of 216 patients with keloids were collected from Department of Dermatology, the First Affiliated Hospital of Kunming Medical University from 2016 to 2019. Total DNA was extracted from peripheral blood samples of all the patients, as well as keloid tissues and perilesional normal skin tissues of 25 patients with keloids. Peripheral blood samples were collected from 299 health checkup examinees without keloids in Health Examination Center, the Affiliated Hospital of Yunnan University, who served as controls. PCR amplification and Sanger sequencing were performed on the mtDNA D-loop region, and mutation sites in each sample were analyzed by comparisons with the revised Cambridge Reference Sequence (rCRS) . Haplogroups were assigned in the 2 groups by using Phylotree-mtDNA tree Build 17. Mutations in the mtDNA D-loop region were compared among keloid tissues, perilesional normal skin tissues and peripheral blood samples. A median-joining network was constructed via network 5.0 software. Binary logistic regression analysis was performed to investigate the correlation between haplogroup frequencies and the occurrence of keloids, and chi-square, t and t′ tests were used to analyze clinical data. Results:Among the 216 patients with keloids, variations in mtDNA D-loop region were classified into 10 haplogroups, including A, B, D, R9, G, M*, M7, M8, M9 and N9, with the haplogroups R9 and M9 showing the highest (21.3%, 46/216) and lowest (0.9%, 2/216) frequencies respectively. The frequencies of haplogroups M7 ( P=0.040, OR=0.248, 95% CI: 0.066 - 0.937) and N9 ( P=0.048, OR=0.191, 95% CI: 0.037-0.986) were significantly lower in the patients with keloids than in the controls. The median-joining network plot showed that the distribution pattern of the haplogroup M7 differed between the patients with keloids and controls. Significantly less number of lesional sites and younger age of onset were observed in the patients with haplogroup M7 compared with those with non-M7 haplogroups ( P=0.000 1, 0.045, respectively) . Conclusion:The haplogroup M7 is correlated with the occurrence of keloids, and may be a potential protective factor for keloid formation.

Objective:To collect the simple interventions in pediatric biomedical research and analyze the risk condition, to establish the minimal risk evaluation criteria, thus to provide the scientific method for the ethical re-view of pediatric biomedical research. Methods:The expert consultation was carried out on the minimal risk evalu-ation of the simple interventions for pediatric biomedical research, and 25 experts from 11 medical institutions car-rying out children' s clinical research were selected to conduct 2 rounds of expert consultation. Results:25 valid questionnaires were collected, and the positive coefficient of the respondents was 100％. The judgment and famili-arity or degree of attention on the related problems was 0 . 764 . The minimal risk evaluation criteria of 25 simple in-terventions in 4 dimensions were determined. Conclusion: We determine the minimal risk evaluation criteria for simple interventions in pediatric biomedical research using the Delphi method, and the research results were relia-ble and could provide a reference for the ethical review of pediatric biomedical research.

With human placed in the whole nature, by following the biologic evolution path, the property of channel structure for "imprinting template" in meridian andwas explored with supramolecular chemistry. In the history of biologic evolution, each molecule in "molecule society" gradually developed into various highly-ordered supramolecular bodies based on self-identification, self-assembly, self-organization, self-replicating of"imprinting template", and thereby the original biochemical system was established, and finally evolved into human. In the forming process of supramolecular bodies, the channel structure of"imprinting template" in guest supramolecular bodies would be kept by host supramolecular bodies, and communicate with the outside to exchange materials, energy, information, otherwise life phenomenon could not continue, for which it was the chemical nature of biolo-gical supramolecular bodies for body to develop meridian. Therefore, the human was a gigantic and complicated supramolecules body in biological nature, and possessed the supramolecules "imprinting template" at each stage of evolution, for which the meridians were formed. When meridians converged, acupoints appeared; when acupointsconverged,appeared. With the promotion of the blood from heart, according to"imprinting template", the guest supramolecular bodies and host meridian produced-analysis, which was the-phenomenon of guest in meridian. It presented asimage of physiology and pathology as well as action regularities of medication and acupuncture tolerance, by which current various meridian viewpoints could be explained and propose the hypothesis of meridian supramolecular bodies. The meridian and its phenomenon was decide by its "imprinting template" of supramolecular bodies and self-reaction regularities, which abided through the living nature. This was the substance for meridian biology.