Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

Objective To investigate the role of activating transcription factor 4 (ATF4) in benign prostatic hyperplasia (BPH) in order to elucidate the molecular mechanism underlying BPH progression. Methods Firstly, we analyzed the correlation between the expression of ATF4 and the volume of prostate transition zone in BPH tissues using publicly available datasets. Subsequently, we explored the potential association among ATF4, epithelial-mesenchymal transition (EMT) and BPH through single-cell RNA sequencing (scRNA-seq). Finally, we validated the findings by silencing ATF4 and treating BPH cells with ATF4 protein inhibitors, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, and Western blot. Results The expression of ATF4 in BPH tissues exhibited a significant positive correlation with the volume of prostate transition zone (r=0.64, P＜0.05). scRNA-seq analysis revealed that ATF4 was significantly upregulated in the prostate epithelial cells of BPH patients (P＜0.05), and its expression demonstrated a significant positive correlation with the Hallmark EMT singscore (r=0.14, P＜0.05). In vitro experiments further indicated that knockdown of ATF4 led to a significant reduction in the proliferative activity of BPH-1 cells (P＜0.05). Similarly, inhibition of ATF4 activity resulted in a marked decrease in the proliferative capacity and EMT of BPH-1 cells (P＜0.05). Conclusion ATF4 may exert a promoting effect on BPH by modulating the EMT signaling pathway;therefore, ATF4 may serve as a novel therapeutic target of BPH.

BackgroundFamily factors are known to play a critical role in the development， progression and prognosis of adolescent patients with depressive disorder. Psychodrama group therapy has the potential for bringing about positive change in individual growth and relationship repair， but there is currently insufficient research evidence for the effectiveness of psychodrama group therapy in promoting the recovery in depressive disorder in adolescents through improving the family parenting skills of their parents. ObjectiveTo explore the influence of psychodrama group therapy based on family parenting intervention on parents of adolescent patients with depressive disorder， so as to provide references for promoting the recovery for adolescent patients with depressive disorder. MethodsPurposive sampling was used to recruit adolescent patients who met the diagnostic criteria for depressive disorder of the International Classification of Diseases， tenth edition （ICD-10） and hospitalized in the psychiatric outpatient department of the First Affiliated Hospital of Chongqing Medical University from October 2023 to March 2024， and their parents （either mother or father） were taken as the study subjects. Psychodrama group therapy based on family parenting intervention was performed once a week for 6 consecutive weeks. After intervention， semi-structured interviews were conducted with parents who participated in the group， and the interviews were recorded. Content analysis method was employed to perform qualitative analysis on the interview recordings and verbatim transcripts. ResultsAfter receiving psychodrama group intervention based on family parenting， parents of adolescent patients with depressive disorder demonstrated improvement in emotional state， enhanced reflective ability and altered coping style， which were specifically manifested as reducing negative emotions， increasing positive emotions， reflecting on themselves， empathizing with others， adjusting cognition， changing the way of stress regulation， improving communication styles and actively seeking resources. ConclusionApplication of psychodrama group therapy based on family parenting intervention may improve emotional state， reflective ability and coping style of the parents of adolescent patients with depressive disorder. ［Funded by Chongqing Education Commission Humanities and Social Science Research Project （number， 19SKGH018）； Chongqing Social Science Planning Project （number， 2021WT29）］

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Objective To investigate whether the pyroptosis-related Toll-like receptor 4(TLR4)signaling pathway influences the malignant transformation of actinic keratosis(AK)into cutaneous squamous cell carcinoma(SCC).Methods A total of 6 lesion tissue samples each from patients with AK and SCC,as well as 5 normal skin tissue samples from healthy subjects as controls,were collected from the First Affiliated Hospital of Kunming Medical University between August 2020 and August 2021.Quantitative PCR(qPCR)and Western blot analysis were performed to determine the mRNA and protein expression levels of TLR4 pathway-related factors,including TLR4,CPB1,NLRP3,IL-1β,and IL-18.TLR4/TUNEL double immunofluorescence staining was used to evaluate TLR4 expression and the level of cellular pyroptosis in tissue samples.In addition,Western blotting was performed to analyze the expression differences of pyroptosis-related core proteins(pro-caspase-1,cleaved caspase-1/p20,GSDMD,and cleaved N-terminal GSDMD)and TLR4 among the normal keratinocyte cell line HaCaT and SCC cell lines A431 and SCL-1.Results Quantitative PCR and Western blot results showed that the mRNA and protein expression levels of TLR4,CPB1,NLRP3,IL-1β,and IL-18 were significantly higher in SCC tissues than in AK and normal skin tissues(P<0.05).TLR4/TUNEL double immunofluorescence results revealed a progressive increasing trend in TLR4 expression and pyroptosis levels from normal skin to AK and further to SCC(P<0.05).Furthermore,in SCL-1 cells,the expression levels of pro-caspase-1,cleaved caspase-1/p20,cleaved N-terminal GSDMD,and TLR4 were significantly upregulated(P<0.05),whereas in A431 cells,only TLR4 expression was increased(P<0.05),and the levels of other pyroptosis-related proteins were downregulated compared to HaCaT cells(P<0.05).Conclusion The expression of the TLR4 signaling pathway gradually increased from AK to SCC,and its activation status varied among different cutaneous squamous cell carcinoma cell lines.

Objective:The purpose of this study was to investigate the diagnostic value and clinical significance of cochlear microphonics (CM) combined with otoacoustic emission (OAE) in patients with auditory neuropathy (AN).Methods:The study included patients who were diagnosed with bilateral AN and had CM originating from both sides. The CM amplitude, latency, duration and intensity-amplitude (I/O) function curve were recorded by CM test. According to whether the distortion product otoacoustic emissions (DPOAE) passed through, the patients were divided into three groups: bilateral OAE passed group (OAE PP Group), bilateral OAE failed group (OAE RR Group), and unilateral OAE passed through one side failed group (OAE PR Group). OAE was elicited by four or more frequencies of 750-8 000 Hz. The characteristics of CM and its related influencing factors were analyzed, and data were processed and analyzed by SPSS 26.0 software. Results:(1) A total of 256 patients (512 ears) with AN were enrolled, including 161 patients (322 ears) in OAE PP group, 32 patients (64 ears) in OAE PR group and 63 patients (126 ears) in OAE RR group. OAE failed in 30.9% of patients with AN. (2) When the stimulation intensity was 100 dB nHL, the CM amplitude of OAE passing ear (OAE P+CM P group) in AN patients aged 3 years was 0.43±0.17μV, which was significantly higher than that of OAE not passing ear (OAE R+CM P group) (0.29±0.15) μV ( t=4.876， P<0.001). The CM duration of the OAE P+CM P group was (5.18±1.04) ms, which was longer than that of the OAE R+CM P group at 4.60±1.12 ms ( P=0.005). The I/O function curve of OAE P+CM P group showed a nonlinear trend, while, that of OAE R+CM P group showed a linear trend. (3) In the OAE P+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, disease course, PTA, and ASSR threshold ( P<0.001), with correlation coefficients of r=-0.475, r=-0.519, r=-0.367, r=-0.374, and r=-0.494, respectively. In the OAE R+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, and ASSR threshold ( P<0.05), with correlation coefficients of r=-0.271, r=-0.240, and r=-0.287, respectively. Conclusions:Excluding patients with high-frequency steeply sloping hearing loss, when ABR is absent or abnormal and OAE is absent, CM detection can reduce the rate of missed diagnosis of AN. The analysis of CM amplitude and I/O function curve is helpful to determine the lesion site of AN patients, which is convenient for early diagnosis and effective intervention.

Objective:To analyze the characteristics and significance of traumatic brain injury-related articles published in Chinese Journal of Trauma (hereinafter referred to as"the Journal") from 1985 to 2024. Methods:Using the CNKI database as the data source, traumatic brain injury-related articles published in the Journal from 1985 to 2024 were retrieved. Key metrics analyzed included total publication count, article types [original articles (including basic and clinical research, with clinical research further categorized as prospective/retrospective and single-center/multicenter studies), case reports, reviews/expert forums, consensus/guidelines], publication timeline, provincial and institutional collaborations, authors, and key words.Results:Among 10 687 total publications, 1 579 articles (14.77%) focused on traumatic brain injury, comprising comprised 1 196 original articles (75.74%), 226 ase reports (14.31%), 151 reviews/expert forums (9.56%), and 6 consensus/guidelines (0.38%). When stratified by decade (1985-1994, 1995-2004, 2005-2014, 2015-2024), the proportion of basic research among original articles was 12.67%, 28.13%, 31.70%, and 37.32%, respectively. Of clinical studies, prospective designs accounted for 23.39%, 34.21%, 34.73%, and 51.69%, respectively and multicenter collaborations accounted for 17.74%, 27.96%, 33.83%, and 47.19%, respectively. The number of case reports was 38, 142, 27, and 19, respectively; the number of reviews/expert forums was 4, 17, 53, and 77, respectively; and the number of consensus and guidelines was 0, 0, 1, and 5, respectively. The regions with more than 150 published articles were Shanghai Municipality, Zhejiang Province and Chongqing Municipality. The top 3 prolific institutions in the last two decades were Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (46 articles), Huashan Hospital Affiliated to Fudan University (26 articles), and Changzheng Hospital Affiliated to Naval Medical University (25 articles). The top 3 prolific authors were Jiang Jiyao (66 articles), Zhang Sai (40 articles), and Zhu Cheng (38 articles). Beyond "brain injury", the top five key words were "treatment", "prognosis", "intracranial pressure", "brain edema", and "therapeutic hypothermia". Among the top 20 key words, "intracranial pressure" was the only specific monitoring metric, while "therapeutic hypothermia" and "decompressive craniectomy" were the most frequently cited specific treatment and surgical procedure, respectively.Conclusion:Over the 40-year period, the Journal′s traumatic brain injury-related articles have demonstrated a rising proportion of basic research among original articles, increased adoption of prospective and multicenter designs in clinical studies, and substantial growth in reviews/expert forums alongside consensus/guidelines in recent years, with research output concentrated among a limited number of institutions and authors.

This case report introduces Professor ZOU Wei 's experience of treating a patient with Wernicke encephalopathy using the "regulating spirit and promoting yang acupuncture method". The patient was diagnosed as spleen and stomach deficiency with internal liver wind. The treatment principle focused on regulating spirit and awakening the brain, strengthening the spleen, calming wind, and relaxing the tendons. Three groups of acupoints were selected: ①acupoints for awakening the brain by regulating spirit and unblocking meridians (Baihui [GV20], Qianshencong [EX-HN1] and bilateral Taiyang [EX-HN5], Fengchi [GB20]), etc.; ②acupoints for harmonizing the spleen, stomach, qi, and blood (bilateral Tianshu [ST25], Daheng [SP15], Taixi [KI3], etc.); ③acupoints for relaxing and softening the tendons (bilateral Waiguan [TE5], Hegu [LI4], Yanglingquan [GB34], Xuanzhong [GB39]).The needles were retained for 50 min per session, once daily, 7 days a week. After 16-week treatment, the patient was able to walk a few steps slowly with assistance, and other symptoms returned to normal. A two-month follow-up showed the patient's condition remained stable, walking distance further increased, and overall health significantly improved.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Wernicke Encephalopathy/physiopathology*