OBJECTIVE To investigate the effects of total flavonoids from Carthamus tinctorius L. （TFCTL） on hepatic stellate cell （HSC） activation based on the microRNA （miRNA）-204/NUAK family SNF1-like kinase 1 （NUAK1）/Hippo signaling axis， thereby elucidating the potential mechanism underlying their antifibrotic effects. METHODS The HSC-T6 cells were divided into control group， model group， TFCTL low-concentration group （20 μg/mL）， TFCTL medium-concentration group （40 μg/mL）， and TFCTL high-concentration group （60 μg/mL）. Except for control group， the remaining groups were treated with 5 ng/mL of transforming growth factor-β to induce the activation of hepatic stellate cells， followed by the addition of corresponding drug solutions/culture medium and incubation for 24 hours. Cell apoptosis was assessed， the expression levels of α-smooth muscle actin （α-SMA）， type Ⅰ collagen （Collagen Ⅰ） and proteins associated with the Hippo/Yes-associated protein （YAP） pathway [YAP， large tumor suppressor kinase 1 （LATS1）， and mammalian STE20-like kinase 1 （MST1）] were detected. Additionally， cell transfection was used to investigate the activity of the miRNA-204/NUAK1/Hippo signaling axis at both the genetic and protein levels. RESULTS After intervention with TFCTL， the apoptosis rate of HSC-T6 cells and the protein expressions of MST1 （except for the TFCTL high-concentration group） and LATS1 were significantly increased （P＜0.05）， while the protein expressions of α-SMA， CollagenⅠ， and YAP （except for the TFCTL medium-concentration group） were significantly decreased （P＜0.05）. Further results from cell transfection experiments revealed that after transfection with miRNA-204 mimics， the mRNA it’s protein expressions of α-SMA， CollagenⅠ， NUAK1， and YAP in HSC-T6 cells were significantly decreased （P＜0.05）， while the mRNA and protein expressions of LATS1 and the mRNA expression of MST1 were significantly increased （P＜0.05）. Conversely， the results were opposite following transfection with miRNA-204 inhibitors. CONCLUSIONS TFCTL can exert anti-hepatic fibrosis effects by up-regulating the expression of miRNA-204， thereby down- regulating the expressions of NUAK1， inactivating the Hippo/YAP pathway， which in turn suppresses the activation of HSC and promotes their apoptosis.

ObjectiveTo explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment（MCI）. MethodsBased on the baseline survey of the Hubei memory and aging cohort study（2018-2023）， the participants completed a thorough neuropsychological assessment and physical examination， and self-reported a history of general anesthesia and surgery. The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model. In addition， the stratification and interaction analysis of anesthesia history， anesthesia number and physical intellectual exercise were conducted separately. ResultsA total of 5 069 older adults aged 65 and above were included in this study， including 3 692 city dwellers and 1 377 rural people， among whom were 2 584 women （51%）. Out of the 1 472 participants with history of general anesthesia， 249 people （17.4%） had MCI. After controlling for confounding factors， there was a 39.6% increased risk of MCI in older adults who underwent general anesthesia ［OR=1.396，95%CI（1.169，1.668），P<0.001］， suggesting that general anesthesia may be an independent influence on MCI. For the older adults who had one general anesthesia ［OR=1.235，95%CI（1.001，1.523），P=0.049］， two general anesthesia ［OR=1.779，95%CI （1.292，2.450），P<0.001］， and three OR more general anesthesia ［OR=2.395，95%CI （1.589，3.610），P<0.001］， their risks of MCI were increased by 23.5%， 77.9%， and 139.5%， respectively. Compared with the older adults without a history of general anesthesia who did not exercise， the risk of developing MCI was significantly negatively correlated with the exercise group， cognitive exercise group， and combined exercise and cognitive exercise groups （all P<0.001）. The risk of developing MCI in the exercise group was 60.2% of that in the no exercise group ［OR = 0.602， 95% CI（0.456， 0.795）］， the risk in the cognitive exercise group was 42.4% of that in the no exercise group ［OR = 0.424， 95% CI（0.294， 0.613）］， and the risk in the combined exercise and cognitive exercise group was 27.0% of that in the no exercise group ［OR = 0.270， 95% CI （0.208， 0.353）］. In the older adults with a history of general anesthesia， compared with the no exercise group， the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group （all P < 0.05）. The risk of developing MCI in the cognitive exercise group was 47.7% of that in the no exercise group ［OR=0.477， 95% CI （0.256，0.892）］， the risk in the combined exercise and cognitive exercise group was 34.5% of that in the no exercise group ［OR=0.345， 95% CI （0.220， 0.540）］， while the risk in the exercise-only group did not show a significant difference. ConclusionThe risk of MCI increased significantly in older adults with a history of general anesthesia， and this risk increased with the times of anesthesia. Physical and mental exercise reduces the risk of MCI. it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.

ObjectiveTo observe the clinical efficacy and safety of Dizhuo Huayu prescription combined with catgut embedding therapy in patients with nonalcoholic steatohepatitis （NASH） and dyslipidemia and explore the effect of the combined therapy on inflammatory cytokines interleukin （IL）-18 and IL-1β. MethodsA total of 82 patients with NASH and dyslipidemia from the Gastroenterology Department of the First Affiliated Hospital of Henan University of Chinese Medicine were randomly divided into a control group and a treatment group， with 41 patients in each group. The control group received Polyene Polyenylphosphatidylcholine Capsules， while the treatment group received Dizhuo Huayu prescription granules combined with catgut embedding. The treatment duration was 24 weeks for both groups. At weeks 0， 12， and 24， the traditional Chinese medicine （TCM） syndrome score， body mass index （BMI）， liver fat content assessed by Fibroscan （CAP value）， the level of alanine transaminase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transferase （GGT）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acid （FFA）， and the expression of inflammatory cytokines IL-18 and IL-1β in serum were observed. Adverse reactions in both groups were recorded. ResultsA comparison of the comprehensive therapeutic effects between the two groups after 24 weeks of treatment revealed that the total effective rate was 62.16% （23/37） in the control group and 85.71% （30/35） in the treatment group， with a statistically significant difference （χ² = 5.14， P<0.05）. At weeks 12 and 24 after treatment， the TCM syndrome score， BMI， CAP value， TC， TG， LDL-C， and FFA were all significantly lower in both groups compared to pre-treatment levels， while the HDL-C level significantly increased （P<0.05）. The effect was better at week 24 （P<0.05） than at week 12 （P<0.05）， and the treatment group showed better outcomes than the control group at weeks 12 and 24 after treatment （P<0.05）. After 24 weeks of treatment， both groups exhibited significant reductions in IL-18 and IL-1β levels （P<0.05）. The treatment group demonstrated superior efficacy compared to the control group after treatment （P<0.05）. Both groups experienced decreases in ALT， AST， and GGT levels after treatment （P<0.05）. However， there were no statistically significant differences between the 12-week and 24-week post-treatment values within each group， nor were there significant differences between the two groups. No significant adverse reactions were observed in both groups. ConclusionThe Dizhuo Huayu prescription combined with catgut embedding therapy is safe and effective in treating patients with NASH and dyslipidemia， exhibiting hepatoprotective， anti-inflammatory， lipid-regulating， and weight-reducing effects.

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective To investigate the clinical characteristics of adult secondary hemophagocytic syndrome(sHLH)and analyze the changes and significance of TH17/Treg cells and lymphocyte subsets,providing favorable references for clinical work.Methods 82 a-dult sHLH patients admitted to our hospital from April 2021 to March 2023 were selected.On the second day of admission,we observed their clinical characteristics and detected the levels of TH17/Treg cells(TH17,Treg,TH17/Treg)and lymphocyte subsets(CD3+,CD4+,CD8+,CD19+,CD16+CD56+).The patients were given the HLH-2004 treatment regimen and followed up for 6 months.Ac-cording to the treatment results,they were divided into the survival group(n=57)and fatality group(n=25).The levels of TH17/Treg cells and lymphocyte subsets on the second day of admission between the two groups were compared.The correlation between TH17/Treg cells and lymphocyte subsets and the value of TH17/Treg cells in evaluating the fatality of adult sHLH patients were ana-lyzed.Results All 82 adult sHLH patients had elevated serum beta-2 microglobulin and ferritin levels,and more than 90%of patients had clinical characteristics such as persistent irregular high fever,serous cavity effusion,decreased blood cells,and liver function dam-age.The levels of TH17,TH17/Treg,CD3+,and CD8+T cells on the second day of admission,1 month,2 months,and 3 months after treatment in the survival group were significantly lower than those in the fatality group(P<0.05),while the levels of Treg,CD4+,and CD16+CD56+lymphocytes were the opposite(P<0.05).The area under the reciever operating characteristics curve(AUCROC)of TH17/Treg cells combined with lymphocyte subsets in predicting the fatality of adult sHLH patients was 0.853(95%CI:0.758-0.922),which was higher than that of each individual indicator(P<0.05).Conclusion The clinical characteristics of adult sHLH are complex and diverse,with significant immune dysfunction of TH17/Treg and lymphocyte subsets.The TH17/Treg cells combined with lympho-cyte subsets have high efficacy in predicting the prognosis of adult sHLH patients.

Microneedles (MNs) serve as a revolutionary paradigm in transdermal drug delivery, heralding a viable resolution to the formidable barriers presented by the cutaneous interface. This review examines MNs as an advanced approach to enhancing dermatological pathology management. It explores the complex dermis structure and highlights the limitations of traditional transdermal methods, emphasizing MNs' advantage in bypassing the stratum corneum to deliver drugs directly to the subdermal matrix. The discourse outlines the diverse typologies of MNs, including solid, coated, hollow, hydrogel, and dissolvable versions. Each type is characterized by its unique applications and benefits. The treatise details the deployment of MNs in the alleviation of cutaneous cancers, the administration of inflammatory dermatoses such as psoriasis and atopic dermatitis, and their utility in wound management. Additionally, the paper contemplates the prospects of MNs within the realm of aesthetic dermatology and the burgeoning market traction of cosmetic MN formulations. The review summarizes the scientific and commercial challenges to the clinical adoption of MN therapeutics, including dosage calibration, pharmacodynamics, biocompatibility, patient compliance, sterilization, mass production, and regulatory oversight. It emphasizes the need for ongoing research, innovation, and regulatory harmonization to overcome these obstacles and fully realize MNs' potential in treating skin diseases and improving patient welfare.

The abuse of antibiotics and other antimicrobial drugs has led to a significant increase in the prevalence of bacterial drug resistance. The advent of nanotechnology offers a promising way to address this challenge. Metal nanomaterials have emerged as a prominent class of antimicrobial agents, offering a number of advantages, including ease of preparation, high stability, potent efficacy against drug-resistant bacteria, and low toxicity. In this review, the antibacterial mechanisms of metal nanomaterials and the current research progress of gold, silver, copper, iron, platinum, palladium, and gallium nanomaterials and their application in the field of antibacterial were summarized with the aim of providing reference for the antibacterial use of metal nanomaterials.

Diseases caused by microbial infections, including bacteria, fungi, and viruses, are increasing every year. Currently, antibiotics are the primary treatment method for bacterial infections. However, over use of antibiotics can easily lead to bacterial resistance. Due to the broad-spectrum antibacterial properties of copper nanomaterials, they exhibit excellent antibacterial activity against both gram-negative bacteria and gram-positive bacteria. In this review, the preparation methods of copper nanomaterials were summarized, the antibacterial and antiviral effects of copper nanomaterials, and their applications in the fields of antibacterial and antiviral were discussed. Finally, the problems of copper nanomaterials in terms of toxicity and stability were summarized, and their future applications in the fields of antibacterial and antiviral were prospected.

Objective: To investigate the current situation and related factors of the ecological environment and health literacy level of medical college students in Shiyan City, so as to propose relevant countermeasures and suggestions for improvement in these domains. Methods: From May to June 2023, 1 312 medical students from Hubei University of Medicine in Shiyan City were selected by accidental sampling to investigate the level and influencing factors of the ecological environment and health literacy among this population. The Chi square test and binary multivariate Logistic regression analysis were performed to analyze the different characteristics and main influencing factors of the ecological environment and health literacy levels in this population. Results: The level of the ecological environment and health literacy level among medical students in Shiyan City was 24.3%. Different levels of ecological environmental and health literacy were observed among medical students by gender, grade, major and ethnicity ( χ 2=5.13, 54.87 , 64.71, 5.99, P <0.05). Higher rates were also observed among public health major students than among students of other majors. The first three classification literacy levels consisting of basic literacy, basic knowledge, and basic skills were 4.6%, 49.5 % and 50.4%, respectively. The possession rates of six secondary classification indicators were as follows:basic cognition ( 53.2 %), basic attitudes (34.5%), scientific knowledge (3.0%), behavioral knowledge (22.5%), cognitive skills (59.5%) and operational skills (48.6%). The results of multivariate Logistic regression showed that ethnic minorities and biomedical majors were negatively correlated with medical students ecological environment and health literacy ( OR =0.61,0.52), while female students, public health majors, sophomores and seniors were positively correlated with medical students ecological environment and health literacy ( OR=1.44, 1.95, 2.16, 2.24, P <0.05). Conclusions The overall level of ecological environment and health literacy among medical students in Shiyan City is low. Schools should popularize environmental health knowledge from different perspectives in order to improve the overall literacy level of environmental health literacy among medical students.