Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.

BACKGROUND: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis. METHODS: Restenosis and atherosclerosis rat models of type 2 diabetes ( n   =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis. RESULTS: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. CONCLUSION Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Muscle, Smooth, Vascular/metabolism* ; Rats ; DNA Methylation/physiology* ; CCAAT-Enhancer-Binding Protein-beta/genetics* ; Male ; Myocytes, Smooth Muscle/cytology* ; Rats, Sprague-Dawley ; RNA-Binding Proteins/genetics* ; Cells, Cultured ; Coronary Restenosis/metabolism*

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans ; Aminolevulinic Acid/therapeutic use* ; Skin Neoplasms/pathology* ; Photochemotherapy/methods* ; Female ; Carcinoma, Squamous Cell/pathology* ; Middle Aged ; Photosensitizing Agents/therapeutic use* ; Carcinoma, Basal Cell/drug therapy*

OBJECTIVE To explore the effects of trichloroisocyanuric acid(TCCA)on the prolifera-tion of spermatogonia by inducing oxidative stress and ferroptosis.METHODS GC-1 cells were cultured in DMEM-F12 medium,and cell proliferation was plotted according to the growth curve.GC-1 cells were treated with TCCA at concentrations of 0(cell control),97,194,and 387 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,apoptosis cells were stained with Hoechst 33342,cell cycle was examined by PI staining method,RT-qPCR was performed to measure the mRNA expres-sion levels of apoptosis-related genes Bax,Fas,oxidative stress-related genes superoxide dismutase 2(SOD2),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),dihydroorotate dehydrogenase(DHODH),DNA methyltransferase 3A(DNMT3A),and DNA methyltransferase 3L(DNMT3L).The Griess method was used to determine the nitric oxide(NO)content,colorimetric method for the malondialdehyde(MDA)level,DCFH-DA fluores-cence probe method for the reactive oxygen species(ROS)level,DNTB colorimetric method for the reduced glutathione(GSH)content,and WST-8 method for the reduced coenzymeⅡ(NADPH)content.RESULTS Compared with the cell control group,the cell survival rates in the TCCA 194 and 387 μmol·L-1 groups decreased significantly(P<0.01),accompanied by nuclear condensation and fragmentation,a significant increase in apoptosis rate(P<0.01),and cell arrest in the G2/M phase(P<0.05).Additionally,in the TCCA 387 μmol·L-1 group,the levels of NO,MDA and ROS increased(P<0.01),while the levels of GSH and NADPH decreased(P<0.01).Moreover,the mRNA expressions of SOD2,GPX4,Nrf2,SLC7A11,and DHODH decreased(P<0.05,P<0.01),while the expressions of Bax,Fas,DNMT3L,and DNMT3A increased(P<0.05,P<0.01).CONCLUSION TCCA exposure reduces the viability of GC-1 cells,inhibits cell proliferation,induces apoptosis of GC-1 cells.The mechanism may be related to the ability of TCCA to enhance oxidate stress,induce ferroptosis,and interfere with the methylation of GC-1 cells.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The clinical and genetic characteristics of the family reported with neurodevelopmental syndrome caused by the SPTBN1 gene mutation were analyzed for clinical diagnosis.The proband was a boy, 2 years and 3 months old, admitted to the Department of Neurology, Guangzhou Women and Children′s Medical Center in June 2022 with comprehensive developmental delays as the main manifestation.The boy was backward in development since childhood.He was able to raise his head at the age of 3 months and sit alone at the age of 11 months.He could stand up with support but was unable to climb.He occasionally spoke polysyllabic words.The proband′s elder brother, 3 years and 1 month old, was able to walk at the age of 1 year and 6 months, and could speak " Mom and Dad" consciously and understand some instructions.He liked to play with other children.The mother of the proband was mentally retarded, while the father and grandparents of the proband had no symptoms.The proband was found to have a heterozygous mutation of the SPTBN1 gene (NM_003128.3), c.811G>A (p.Val271Met).The proband′s mother and elder brother also had a heterozygous mutation, which, however, was not detected in the proband′s father.The neurodevelopmental syndrome caused by the SPTBN1 gene mutation is rare in China, which can be manifested as language and motor delays and intellectual disabilities from early childhood, and individuals with the same genetic variation show different clinical phenotypes.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

OBJECTIVE To study the inhibitory effect and mechanism of curcumin and its derivatives A and B on TGF-β induced LX-2 cell fibrosis. METHODS Established the liver fibrosis model of LX-2 cells induced by TGF-β(10 ng·mL−1).The effects on cell proliferation were detected by CCK-8. The effects on cell apoptosis was detected by flow cytometry. The effects on fibrosis related factors(Collagen I, Collagen Ⅳ, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, MMP2, MMP9, TIMP1 and TIMP2) protein expression and gene transcription levels were detected by Western blotting and q-PCR. RESULTS The curcumin and its derivative A and B had the inhibition effects on normal LX-2 cells, and the IC25 values were 15.7, 2.6, 10.2 μmol·L−1, respectively. Compared to the model group, the curcumin(15.7 μmol·L−1) and its derivative A(2.6 μmol·L−1) and B(10.2 μmol·L−1) had the significant inhibition effects on cell proliferation of the TGF-β induced LX-2 cells(P<0.05). The cell apoptosis rate of curcumin derivative B group was higher than the model group(P<0.05). Collagen I, Fibronectin, Vimentin, α-SMA, TGFβR1 and TIMP-1 protein expression levels in curcumin group were lower, while the protein expression level of MMP-9 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, TIMP-1 and TIMP-2 in curcumin derivative A group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, TIMP-1 and TIMP-2 in curcumin derivative B group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The gene transcription levels of Collagen I, Fibronectin, α-SMA and TIMP-1 in curcumin group were lower(P<0.05). The gene transcription levels of Collagen I, Fibronectin and α-SMA in curcumin derivative A and B groups were lower(P<0.05). CONCLUSION Curcumin and its derivatives A and B inhibit the abnormal activation and proliferation of TGF-β-induced LX-2 cells, inhibit the excessive secretion and accumulation of its extracellular matrix components, and promote its degradation, thus playing an anti-fibrotic effect in vitro, especially the curcumin derivative B.