BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To understand phenotype conversion in patients with first-episode depression over a 7-year period,to explore the longitudinal disease characteristics and functional outcomes of transitions and non-transitions,and to further analyse the relevant factors affecting transitions.Methods A total of 346 patients with Hamilton depression scale-17(HAMD-17)score≥18,aged 18-60 years and a single episode of major depressive disorder were included in the study.They were follow-up for 7 years to assess their natural history including demographic data,disease characteristics,whether transitions to manic occurred,treatment status.At the end of the 7-year follow-up,treatment emergent symptom scale(TESS),medication adherence rating scale(MARS),and global assessment function(GAF)were used to evaluate adverse reactions,compliance to medication,and patient's overall functional level.Patients were divided into two groups based on the occurrence of mania or hypomania episodes during the 7-year period:the conversion group(those who developed episodes)and the non-conversion group(those who did not).Results A total of 138 patients were followed up for 7 years,including 54 patients(39.1%)in the conversion group and 84 patients(60.9%)in the non-conversion group.When the first episode was enrolled at baseline,the age of first episode was earlier in the conversion group than in the non-conversion group[(27.63±9.63)years vs.(41.20±11.92)years],and there were differences in marital status(unmarried 40.7%vs.7.1%,first marriage 53.7%vs.85.7%,remarriage 3.7%vs.2.4%,separated/divorced 0.0%vs.2.4%,widowed 1.9%vs.2.4%).The proportion of patients with precipitating factors was lower in the conversion group(29.6%vs.48.8%)and shorter duration of untreated psychosis(DUP)[60(15,90)d vs.90(30,180)d].The treatment method in the conversion group had lower only used antidepressant drugs(61.1%vs.81.0%)and more antidepressant combined with mood stabilizers(31.5%vs.16.7%)(all P<0.05).In the 7 years,total number of episodes in the conversion group was more than in the non-conversion group(4.33±1.21 vs.2.70±1.25,P<0.05).By the end of 7 years,the GAF score was lower in conversion group than in the non-conversion group(66.57±8.22 vs.69.21±7.20,P<0.05).Dichotomous unconditional logistic regression analyses revealed that age at first episode(OR=1.109,95%CI:1.058-1.161,P<0.001),DUP(d)(OR=1.005,95%CI:1.001-1.009,P=0.017),was an independent influencing factor on conversion over a 7-year period in patients with first-episode depressive disorders.Conclusion The rate of conversion over 7 years in patients with first-episode depressive disorder is 39.1%in the present cohort and converted patients had relatively earlier age of onset,more pre-onset without inducement,shorter DUP(d),more recurrence,higher the rate of combined treatment and worse overall functional outcome.

Objective:To explore the application effects of the blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" in Medical Immunology. Methods:Eight-year program clinical medical students who were enrolled at Peking Union Medical College in 2016, 2017, and 2018 were selected as the research subjects. An anonymous questionnaire survey was used to analyze students' multidimensional evaluations of the new teaching methodology. The percentage of frontier hotspot topics in the "Immunology Forum" was used to analyze the students' mastery of cutting-edge knowledge in immunology. The number of "Immunology Forum" related "College Students Innovative Training Plan Program" from 2020 to 2023 was used to analyze the effectiveness of this new teaching method in cultivating students' scientific research and innovation abilities. Statistical analysis was conducted using SPSS 25.0 software, and the normality of all continuous variables was assessed using the Shapiro-Wilk test.Results:The questionnaire survey showed 100.00% satisfaction with the course and 95.90% recognition of the new teaching method. More than 90% of students agreed that the new teaching method improved their learning ability, research ability, innovation ability, internal drive, and academic communication ability. The average proportion of hotspot topics in the "Immunology Forum" was 90.37%±7.12%, which was significantly higher than the proportion of non-hotspot topics (5.67%±3.12%). The average number of topics related to "Immunology Forum" in the "College Students Innovative Training Plan Program" was 17.67±1.15 per session, which was significantly higher than the number of topics not related to "Immunology Forum" (8.00±1.73).Conclusions:The blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" can help students timely grasp the cutting-edge knowledge of immunology, cultivate their learning ability, internal drive, academic communication ability, innovation ability, and research ability, and lay a foundation for students to further explore their scientific research and innovation activities.

Cell is the most basic unit of life,and normal metabolism is the key to cell growth and development.Reactive oxygen species(ROS)are important regulators of cell function,and hypoxi-a-inducible factor-1 alpha(HIF-1α)is a ROS receptor,which can activate transient receptor poten-tial vanilloid(TRPV)channel.TRPV is a sensor for temperature,pain,and osmotic pressure.Changes in the environment can induce changes in the activity of TRPV channel,which regulates various physiological and pathological processes of cells through its downstream signaling path-ways.Low temperature plasma can regulate cellular TRPV channel activity through HIF-1α.This article mainly reviews the effect of HIF-1α on cell function through TRPV channel,which has ref-erence significance for future research on various diseases related to TRPV channel and their pre-vention and treatment,as well as provides a new idea for using low temperature plasma technology to treat diseases through regulating TRPV channel.

AIM:A mouse model of acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF)was estab-lished.METHODS:One hundred and twenty male C57BL/6 mice were randomly divided into a negative control group,an IPF group,and an acute exacerbation of interstitial fibrosis(AE-IPF)group.The IPF group received a low dose(3 mg/kg)of bleomycin(BLM)by endotracheal drip on days 0,14,and 28.The AE-IPF group received a high dose(5 mg/kg)of BLM by endotracheal drip on day 56.The control group received an equal volume of saline at different time points.The AE-IPF group was injected with a high dose(5 mg/kg)of BLM via tracheal drip on day 56 on top of the initial IPF induction,while the control group received equal amounts of saline at different time points.Experiments were con-ducted on the 57th,59th,63rd,and 70th days after the initial modeling.Mice were observed for general conditions,CT imaging changes,HE,and Masson staining to assess the degree of alveolitis and fibrosis in lung tissues.Lung function,hydroxyproline(HYP)content in lung tissues,and interleukin-6(IL-6)content in bronchoalveolar lavage fluid(BALF)were also measured.RESULTS:Mice in the AE-IPF group exhibited wheezing,shortness of breath,dyspnea,and weight loss.CT imaging revealed that IPF group mice showed patchy,subpleural reticular fuzzy shadows with irregular thickening of interlobular septa and intralobular linear shadows,along with tractional bronchiectasis.In the AE-IPF group,new ground-glass shadows and solid shadows appeared in addition to the IPF features.AE-IPF group mice demon-strated decreased lung function,elevated lung index,and acute pulmonary edema.HE and Masson staining of AE-IPF group mice showed consistent pathological manifestations of AE-IPF.HYP content in lung tissues,total cell count in BALF,and IL-6 concentration were significantly higher in the AE-IPF group compared to the control group(P<0.05).CONCLUSION:The use of multiple tracheal drip administrations of bleomycin successfully established an AE-IPF ani-mal model in mice.The 63rd day of the experiment was identified as the optimal observation point,as it exhibited the most significant pathological features and clinical symptoms.This model provides ideal conditions for studying AE-IPF patho-genesis and evaluating therapeutic efficacy.

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

Cell is the most basic unit of life,and normal metabolism is the key to cell growth and development.Reactive oxygen species(ROS)are important regulators of cell function,and hypoxi-a-inducible factor-1 alpha(HIF-1α)is a ROS receptor,which can activate transient receptor poten-tial vanilloid(TRPV)channel.TRPV is a sensor for temperature,pain,and osmotic pressure.Changes in the environment can induce changes in the activity of TRPV channel,which regulates various physiological and pathological processes of cells through its downstream signaling path-ways.Low temperature plasma can regulate cellular TRPV channel activity through HIF-1α.This article mainly reviews the effect of HIF-1α on cell function through TRPV channel,which has ref-erence significance for future research on various diseases related to TRPV channel and their pre-vention and treatment,as well as provides a new idea for using low temperature plasma technology to treat diseases through regulating TRPV channel.

Objective To understand phenotype conversion in patients with first-episode depression over a 7-year period,to explore the longitudinal disease characteristics and functional outcomes of transitions and non-transitions,and to further analyse the relevant factors affecting transitions.Methods A total of 346 patients with Hamilton depression scale-17(HAMD-17)score≥18,aged 18-60 years and a single episode of major depressive disorder were included in the study.They were follow-up for 7 years to assess their natural history including demographic data,disease characteristics,whether transitions to manic occurred,treatment status.At the end of the 7-year follow-up,treatment emergent symptom scale(TESS),medication adherence rating scale(MARS),and global assessment function(GAF)were used to evaluate adverse reactions,compliance to medication,and patient's overall functional level.Patients were divided into two groups based on the occurrence of mania or hypomania episodes during the 7-year period:the conversion group(those who developed episodes)and the non-conversion group(those who did not).Results A total of 138 patients were followed up for 7 years,including 54 patients(39.1%)in the conversion group and 84 patients(60.9%)in the non-conversion group.When the first episode was enrolled at baseline,the age of first episode was earlier in the conversion group than in the non-conversion group[(27.63±9.63)years vs.(41.20±11.92)years],and there were differences in marital status(unmarried 40.7%vs.7.1%,first marriage 53.7%vs.85.7%,remarriage 3.7%vs.2.4%,separated/divorced 0.0%vs.2.4%,widowed 1.9%vs.2.4%).The proportion of patients with precipitating factors was lower in the conversion group(29.6%vs.48.8%)and shorter duration of untreated psychosis(DUP)[60(15,90)d vs.90(30,180)d].The treatment method in the conversion group had lower only used antidepressant drugs(61.1%vs.81.0%)and more antidepressant combined with mood stabilizers(31.5%vs.16.7%)(all P<0.05).In the 7 years,total number of episodes in the conversion group was more than in the non-conversion group(4.33±1.21 vs.2.70±1.25,P<0.05).By the end of 7 years,the GAF score was lower in conversion group than in the non-conversion group(66.57±8.22 vs.69.21±7.20,P<0.05).Dichotomous unconditional logistic regression analyses revealed that age at first episode(OR=1.109,95%CI:1.058-1.161,P<0.001),DUP(d)(OR=1.005,95%CI:1.001-1.009,P=0.017),was an independent influencing factor on conversion over a 7-year period in patients with first-episode depressive disorders.Conclusion The rate of conversion over 7 years in patients with first-episode depressive disorder is 39.1%in the present cohort and converted patients had relatively earlier age of onset,more pre-onset without inducement,shorter DUP(d),more recurrence,higher the rate of combined treatment and worse overall functional outcome.