ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

OBJECTIVE: To investigate the influencing factors of pathological positive surgical margins (PSM) after radical resection of prostate cancer. METHODS: The clinical data of 407 patients who underwent radical resection of prostate cancer in our hospital from 2011 to 2020 were retrospectively analyzed. And the patients were divided into two groups according to postoperative pathological results. Single factor analysis was used to evaluate the differences in postoperative Gleason score, preoperative total prostate-specific antigen (tPSA), preoperative serum free prostate-specific antigen to preoperative tPSA ratio (fPSA/ tPSA), clinical stage, postoperative pathological stage, operation method, age, body mass index (BMI), diameter and volume of prostate tumor. Multivariate logistic regression was used to determine the independent risk factor of PSM. RESULTS: Among 407 patients with prostate cancer, 179 cases (43.98%) were positive. Univariate analysis showed that there were significant differences in postoperative Gleason score, preoperative tPSA, clinical stage and postoperative pathological stage between the two groups (P<0.05). And Gleason score, preoperative tPSA and pathologic stage were independent risk factors for PSM. CONCLUSION There are relationships between PSM and postoperative Gleason score, tPSA, clinical T stage, postoperative pathologic pT stage. Among them, postoperative Gleason score (Gleason=7 points, Gleason≥8 points), preoperative total prostate-specific antigen (tPSA > 20 μg/L), and postoperative pathologic pT stage (pT3a, pT3b) were independent risk factors for positive pathological margins of prostate cancer.
Margins of Excision ; Prostatic Neoplasms/surgery* ; Prostatectomy/statistics & numerical data* ; Prostate/surgery* ; Retrospective Studies ; Neoplasm Grading/statistics & numerical data* ; Prostate-Specific Antigen/blood* ; Neoplasm Staging/statistics & numerical data* ; Postoperative Period ; Risk Factors ; Humans ; Male

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Objective:To investigate the preventive and therapeutic effects of iridoid glycosides from Boschniakia rossica(IGBR)on precancerous lesions of liver cancer in rats,and to clarify its possible mechanism.Methods:Thirty Wistar rats were selected and the precancerous liver lesion model was established using the modified Solt-Faber method.The rats were randomly divided into sham operation group,model group,and IGBR group,and there were 10 rats in each group.The morphology of liver tissue of the rats in various groups were observed;the liver weights,liver indexes and liver regeneration degrees of the rats in various groups were measured;HE staining was used to observe the pathomorphology of liver tissue of the rats in various groups;immunohistochemistry method was used to detect the expression of glutathione-S-transferase(GST)-Pi protein in liver tissue of the rats in various groups;colorimetric method was used to detect the activities of γ-glutamyl transpeptidase(γ-GT),catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GST),and the level of malondialdehyde(MDA)in liver tissue and mitochondria of the rats in various groups;Western blotting method was used to detect the expression levels of α-smooth muscle actin(α-SMA),collagen type Ⅰ alpha 1 chain(ColⅠα1),matrix metalloproteinase(MMP)13,MMP2,tissue inhibitor of metalloproteinase(TIMP)1,TIMP2,transforming growth factor β1(TGF-β1),TGF-β1 receptor(TβR),mothers against decapentaplegic homolog(Smad)2/3,Smad4,and Smad7 proteins in liver tissue of the rats in various groups.Results:Compared with sham operation group,the liver weight,liver index and degree of liver regeneration of the rats in model group were increased(P<0.05);compared with model group,the liver weight and liver index of the rats in IGBR group showed a decreasing trend,but the difference was not statistically significant(P>0.05).The HE staining results showed that the liver lobule structure in sham operation group was intact and clear,with large hepatocytes,abundant eosinophilic cytoplasm,and hepatocytes arranged in single cords radiating from the central vein;there were irregular hepatic sinusoids between plates,with only a small amount of collagen fibers and inflammatory cell infiltration in the portal area,and no degeneration or necrosis of hepatocytes.In model group,the normal arrangement of hepatocytes disappeared,the liver lobule structure was disrupted,small cell hyperplasia(mainly oval cells)was observed in the portal area,with massive collagen deposition and significant fibrous tissue hyperplasia in the fibrous septum;hepatocytes showed extensive degenerative edema,hydropic degeneration or even ballooning degeneration and focal necrosis;basophilic hepatocytes formed proliferative areas with clear cytoplasm,centrally located nuclei and 1-2 prominent nucleoli;glassy hepatocytes with enlarged nuclei and pale transparent cytoplasm were also observed.In IGBR group,the liver lobule structure was basically preserved,with reduced inflammatory lesions,mild edema,and scattered spotty or focal necrosis;nuclear atypia and pathological mitotic figures or binucleation were observed.The immunohistochemistry results showed GST-Pi protein positive foci with brown-yellow cytoplasmic staining in round or oval nodules.The GST-Pi protein positive foci were observed in liver tissue of the rats in model group,indicating successful establishment of precancerous liver lesion model.The scattered GST-Pi protein positive foci were observed in IGBR group,which were significantly reduced compared with model group.Compared with sham operation group,the activity of γ-GT in liver tissue of the rats in model group was increased(P<0.05);compared with model group,the activity of γ-GT in liver tissue of the rats in IGBR group was decreased(P<0.05).Compared with sham operation group,the GST activity and MDA level in liver tissue and liver mitochondria of the rats in model group were increased(P<0.05),while the activities of SOD,CAT,and GSH-Px were decreased(P<0.05);compared with model group,the GST activity and MDA level in liver tissue and liver mitochondria of the rats in IGBR group were decreased(P<0.05),while the activities of SOD,CAT,and GSH-PX were increased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of α-SMA,ColⅠα1,TIMP1,and TIMP2 proteins in liver tissue of the rats in model group were increased(P<0.05),while the expression levels of MMP13 and MMP2 proteins were decreased(P<0.05),and the ratios of TIMP1/MMP13 and TIMP2/MMP2 were increased(P<0.05);compared with model group,the expression levels of α-SMA,ColⅠα1,and TIMP2 proteins in liver tissue of the rats in IGBR group were decreased(P<0.05),while the expression levels of MMP13 and MMP2 proteins were increased(P<0.05),and the ratios of TIMP1/MMP13 and TIMP2/MMP2 were decreased(P<0.05).Compared with sham operation group,the expression levels of TGF-β1 and Smad2/3 proteins in liver tissue of the rats in model group were increased(P<0.05);compared with model group,the expression levels of TGF-β1,Smad2/3 and Smad 4 proteins in liver tissue of the rats in IGBR group were decreased(P<0.05).Conclusion:IGBR can inhibit precancerous liver lesions and liver fibrosis in rats,and its mechanism may be related to enhancing the antioxidant capacity of liver tissue,inhibiting TGF-β/Smad signaling pathway and regulating TIMP/MMP balance.

Objective:To analyze the epidemiological characteristics and pathogen spectrum of influenza outbreaks in Shaanxi Province from 2014 to 2023 and provide basis reference for strengthening regional influenza prevention and control.Methods:The data were collected from the Public Health Emergency Management Information System of the China Disease Prevention and Control Information System and the China Influenza Surveillance Information System. On-site epidemiological investigation information and etiological test results of influenza network laboratories reported in Shaanxi Province during 2014-2023 were collected, and descriptive analysis was conducted on the time, region, and location distribution of influenza outbreaks. SPSS 25.0 software was used for statistical analysis.Results:A total of 386 influenza outbreaks were reported in Shaanxi from 2014 to 2023, with a total attack rate of 1.81% (14 880/821 001). The epidemic peaks mainly occurred in winter and spring (November to March of the following year), and there was an alternating pattern of epidemic peaks in different years (the early peak was in December, and the late peak was in March of the following year). The epidemic areas were mainly concentrated in the Qinba Mountains of southern Shaanxi (209, 54.15%) and Guanzhong Plain (173, 44.82%). The epidemic places were mainly distributed in primary schools (239, 61.92%), and the differences of epidemic areas and places were statistically significant (all P<0.001). Influenza A(H3N2) viruses were the predominant pathogen in the outbreak (849, 57.76%), and influenza A(H3N2), B (Victoria) lineage and A(H1N1)pdm09 virus alternately dominated the epidemic peak in different years. Conclusions:The peak of influenza outbreaks in Shaanxi Province was winter and spring during 2014-2023. Primary schools in the Qinba Mountains of southern Shaanxi and Guanzhong Plain should be targeted for prevention and control. In the prevention and control programs, close attention should be paid to the changing trend of dominant strains. Effective intervention measures should be targeted to the high-incidence areas and seasons.

Lasers are widely utilized in ion sources for mass spectrometry.They can be employed to desorb and ionize samples directly or enhance the ionization efficiency of neutral molecules through post-ionization.To investigate the ionization characteristics of the single photon ionization technique,in this work,a femtosecond laser with a wavelength of 515 nm was utilized for desorption,and a nanosecond laser with a wavelength of 118 nm for post-ionization.A laboratory-built laser desorption/laser post-ionization time-of-flight mass spectrometer(LDPI-TOFMS)was used to analyze three types of organic substances including acridines,phenothiazines,and metal porphyrins.The results demonstrated that the single photon ionization method effectively reduced the fragment generation,safeguarded the molecular ions against fragmentation,and achieved soft ionization as indicated by the adductive and characteristic molecular ions.Furthermore,a 266-nm nanosecond laser was employed as a multiphoton post-ionization source for comparison.The outcomes indicated that molecules were significantly fragmented,and more fragmented ions were generated due to the multiphoton ionization technique,which complicated the spectral analysis.The comparison further demonstrated that the single-photon post-ionization technology could be utilized to analyze a variety of organic compounds via soft ionization.LDPI-TOFMS procedure was straightforward,and did not require intricate sample preparations.The laser desorption with single photon post-ionization mass spectrometry showed potential to offer a high level of sensitivity and specificity for surfaces,thin layers,and complicated sample analysis.

Objective:To observe the clinical efficacy and safety of Tongren Niuhuang Qingxin Pills combined with telmisartan tablets in the treatment of hypertensive vertigo syndrome of phlegm-heat disturbance.Methods:Randomized controlled trial was conducted. Totally 80 patients with hypertension vertigo and phlegm-heat disturbance syndrome were selected from March 2021 to August 2022 at Beijing Tongrentang Hospital of Traditional Chinese Medicine as the observation objects. They were randomly divided into two groups using a random number table method, with 40 cases in each group. The control group received oral telmisartan tablets, while the experimental group received Tongren Niuhuang Qingxin Pills in addition to the control group. Both groups were treated for 28 days and followed up for 1 month. The patients' room blood pressure before and after treatment was measured, and TCM syndrome scores were evaluated. The dizziness assessment rating scale (DARS) was used to evaluate the severity of dizziness, adverse reactions during treatment were recorded, drug safety was observed, and clinical efficacy was evaluated.Results:The total effective rate of the experimental group was 85.0% (34/40), and that of the control group was 7.5% (3/40), with statistical significance between the two groups ( χ2=48.32, P<0.001). Compared with before treatment, the experimental group had SBP [(136.63 ± 6.01) mmHg vs. (159.30 ± 9.01) mmHg, t=-21.00] and DBP [(84.48 ± 4.36) mmHg vs. (95.30 ± 3.75) mmHg, t=-13.80] after treatment; after treatment, SBP [(137.34 ± 6.39) mmHg vs. (158.00 ± 10.06) mmHg, t=-5.28] and DBP [(86.08 ± 4.43) mmHg vs. (95.18 ± 6.61) mmHg, t=-8.09] decreased in the control group ( P<0.01), but there was no statistical significance between the two groups after treatment ( P>0.05). After treatment, the TCM syndrome scores in the experimental group (8.68 ± 3.39 vs. 15.12 ± 3.03, Z=-6.61) were lower than those in the control group ( P<0.001), and DARS score [(8.53 ± 3.93) vs. (12.20 ± 3.95), Z=-3.63] was lower than that in the control group ( P<0.001). After treatment, the therapeutic effect index of TCM syndromes in the experimental group improved compared to before treatment in the same group. The therapeutic effect index of each symptom, from high to low, was as follows: rotation of oneself or visual objects>numbness of limbs>dry stool>dizziness and dizziness>liking cold drinks>bitter and dry mouth>red urine>red tongue, yellow coating, and greasy tongue>vomiting sticky and turbid phlegm>tinnitus>smooth pulse. There were no significant adverse reactions during the treatment of the two groups. Conclusion:Tongren Niuhuang Qingxin Pills combined with telmisartan can reduce the blood pressure of patients with hypertensive vertigo syndrome of phlegm-heat disturbance, improve the vertigo symptoms and TCM syndromes of patients, and the efficacy evaluation is superior to that of telmisartan alone.

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.

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.