ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

Objective To explore the correlation between thyroid hormones and massive proteinuria in patients with type 2 diabetes mellitus (T2DM). Methods A total of 308 patients with T2DM admitted to 3201 Hospital between June 2020 and June 2025 were selected as the observation group, and another 250 healthy individuals who underwent physical examinations during the same period served as the control group. The thyroid hormones levels [free triiodothyronine (FT₃), thyroid stimulating hormone (TSH), and free thyroxine (FT₄)] were measured and compared between the two groups. Based on whether 24-hour urinary protein quantification was ≥ 3.5 g, the patients in the observation group were divided into a massive proteinuria group and a non-massive proteinuria group. Multivariate logistic regression analysis was used to analyze the factors influencing the occurrence of massive proteinuria in T2DM patients. Pearson method was applied to analyze the relationship of thyroid hormone indicators with severity indicators of massive proteinuria. Results Compared with the control group and the non-massive proteinuria group, FT₃ and FT₄ in the massive proteinuria group were lower, while TSH was higher (P<0.05). Multivariate logistic regression analysis suggested that glycosylated hemoglobin (OR=1.113, 95%CI: 1.045-1.185), TSH (OR=1.123, 95%CI: 1.006-1.253), eGFR (OR=0.894, 95%CI: 0.822-0.973), and FT₃ (OR=0.898, 95%CI: 0.828-0.973) were related factors for the occurrence of massive proteinuria in T2DM patients (P<0.05). Pearson correlation analysis revealed that FT3 and FT4 levels in T2DM patients were significantly negatively correlated with 24-hour urinary protein quantification (r=-0.514, -0.502), while the level of TSH was positively correlated with 24-hour urinary protein quantification (r=0.486) (P<0.001). Conclusion In T2DM patients, low FT3 and eGFR levels and high TSH and glycosylated hemoglobin levels are related factors for the occurrence of massive proteinuria, and thyroid hormone levels are significantly associated with the severity of massive proteinuria.

ObjectiveTo investigate the alleviating effect of calcium cyanamide （CaCN₂） soil fumigation on replanting problems of Rehmannia glutinosa. MethodsNewly soil （NP） was used as the control group， while three treatment groups were established： replanted soil （RP）， newly soil treated with CaCN₂ （120 g·m²， tillage depth 25 cm） （NPCC）， and replanted soil treated with CaCN₂ （RPCC）. R. glutinosa was cultivated in all groups. At harvest， the tuber agronomic traits （number of enlarged roots， maximum root diameter， fresh weight， dry weight） were measured. The content of catalpol and rehmannioside D was quantified by ultra-high-performance liquid chromatography （UPLC） to evaluate medicinal quality. Rhizosphere soil available nutrients and enzyme activities were analyzed by assay kits. The community structure and composition of fungi and bacteria in rhizosphere soil were assessed via internal transcribed spacer 2 （ITS2） sequencing and 16S rDNA sequencing， respectively. ResultsCompared with NP， the RP group showed obviously reduced in tuber agronomic traits and quality indicators （P0.05）. However， the RPCC group showed significant improvement in agronomic traits and a notable increase in rehmannioside D content compared to RP （P0.05）. The contents of available phosphorus and potassium in RPCC and NP groups were obviously lower than those in RP （P0.05）. The polyphenol oxidase soil （S-PPO） activity in RP was obviously lower than in NP （P0.05）， while sucrose soil （S-SC）， acid phosphatase soil （S-ACP）， and S-PPO activities in RPCC were obviously higher than in RP （P0.05）. Microbial richness and diversity in RP were obviously higher than in NP （P0.05）， whereas no significant differences were observed between the RPCC and NP. The relative abundances of fungal genera Nectria， Myrothecium， Tomentella， and bacterial genus Skermanella were obviousl lower in RPCC and NP than in RP （P0.05）. Correlation analysis that S-ACP activity was positively correlated with the content of rehmannioside D （P0.05）. Fungal genera Engyodontium and Alternaria， and bacterial genera Pir4 lineage， Pirellula， Methyloversatilis， Brevundimonas， Ralstonia， and Acidibacter were obviously positively correlated with tuber dry weight （P0.05）. Conversely， fungal genera Pseudaleuria， Nectria， Haematonectria， Ceratobasidium， and bacterial genera Streptomyces， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated with dry weight （P0.05）. The fungal genus Alternaria and bacterial genera Brevundimonas， Ralstonia， Acidibacter， and Dongia showed positive correlations with medicinal quality of R.glutinosa tuber， while fungal genera Pseudaleuria， Nectria， Stachybotrys， Fusarium， Gibberella， Ceratobasidium， and bacterial genera Sphingomonas， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated （P0.05）. ConclusionCaCN₂ soil fumigation can significantly improve enzyme activities in replanted Rehmannia rhizosphere soil， enhance the utilization of available nutrients， reshape microbial community structure of replanted R.glutinosa at the family and genus level， and notably improve tuber agronomic traits and medicinal quality. This study provides a novel approach to alleviating replanting problems and offers insights for the integrated development of standardized cultivation techniques， including soil disinfection， nutrient-targeted regulation， and microbial inoculant application.

OBJECTIVE To explore the characteristics and influential factors of pharmaceutical clinic service demands， providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted， and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services， while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender， age， educational attainment， and economic burdens， to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%， yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware （P＜0.001）. The demand for pharmaceutical clinic services exhibited a hierarchical characteristic： twelve items were identified as attractive attributes （e. g.， providing suggestions for more affordable treatment options， offering online consultation services， etc.）， five items as expected attributes （e.g.， having a good attitude and being able to patiently answer your questions， etc.）， three items as must-have attributes （e.g.， providing guidance on medication dosage and usage， providing guidance on medication precautions， etc.）， five items as indifferent attributes （e.g.， providing treatment plan recommendations based on the patient’s condition）. There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients （P＜0.001）； patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above （P＝0.016）； those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above （P＝0.011）； patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” （P＝0.002）. CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low； however， those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover， the study also revealed that factors such as gender， age， educational level， and economic burdens exert significant influences on patients’ service demands.

Objective To identify mechanisms regulating disease progression in rat models of pulmonary arterial hy-pertension(PAH).Methods Rat PAH models were established using subcutaneous monocrotaline(MCT)injec-tion and the SU5416/hypoxia(SU/Hx)method.Transcriptomic sequencing of lung tissues was performed to identify gene expression and pathway alterations in PAH rats,followed by a comparative analysis with transcriptomic data of patients with idiopathic pulmonary arterial hypertension(IPAH)in NCBI database.Results Inflammatory-related genes such as CXCL9,CCL24,and SECTM1 were upregulated in both PAH rat models and IPAH patient lungs,while genes such as DGKG and DOCK9 were downregulated(P＜0.05).Pathways related to endothelial cell proliferation regulation and extracellular matrix(ECM)remodeling were significantly upregulated(P＜0.05).Conclusions The imbalance in endothelial cell proliferation and abnormal ECM remodeling may collectively contribute to PAH pathogenesis.Further exploration of these signaling pathways may provide deep in-sights for early diagnosis and targeted therapy of PAH.

Objective:To explore the clinical utility of peripheral immune-inflammatory markers in predicting late-life depression with cognitive impairment(LLD+ CI + ). Methods:A cross-sectional study was conducted between January 2020 and December 2021, collecting demographic data, peripheral blood inflammatory markers, and cognitive function scores from 40 patients with LLD+ CI + , 38 patients with late-life depression without cognitive impairment(LLD+ CI -), and 26 healthy controls(HCs). Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were employed to assess the value of peripheral blood inflammatory markers in differentiating LLD+ CI + . Results:Patients with LLD+ CI + exhibited significantly different levels of lymphocytes, C-reactive protein(CRP), systemic immune-inflammation index(SII), systemic inflammation response index(SIRI), neutrophil-to-high-density lipoprotein cholesterol ratio(NHR), and neutrophil-to-lymphocyte ratio (NLR)compared with the LLD+ CI - group and the HGs group( F=4.000, 11.642, 13.541, 10.441, 6.623, 4.193; P=0.022, 0.003, 0.001, 0.005, 0.036, 0.018). The multivariate logistic regression analysis of factors influencing LLD+ CI + revealed that elevated levels of CRP( OR=4.933, 95% CI: 1.385-17.563, P=0.014), SII( OR=5.534, 95% CI: 1.336-22.927, P=0.018), and NLR( OR=3.386, 95% CI: 1.470-7.797, P=0.004)constitute risk factors for geriatric depression with cognitive impairment, while an increased lymphocyte count( OR=0.206, 95% CI: 0.058-0.725, P=0.014)serves as a protective factor.Further analysis identified CRP, lymphocytes, SII, and NLR as significant predictors for LLD+ CI + , with areas under the curve (AUC) values of 0.849(95% CI: 0.760-0.934), 0.847(95% CI: 0.761-0.933), 0.860(95% CI: 0.777-0.943), and 0.857(95% CI: 0.777-0.938), respectively, in distinguishing LLD with or without cognitive impairment. Conclusions:Peripheral immune-inflammatory markers represent an economical and effective approach for investigating the pathophysiological changes and predictive factors associated with LLD+ CI + .These findings provide valuable insights into the underlying mechanisms and potential therapeutic avenues.

Objective:To observe the clinical efficacy of Xinyue Decoction combined with fluoxetine hydrochloride in the treatment of cognitive impairment of senile depression.Methods:A randomized controlled trial study was conducted. Totally 116 elderly patients with depression accompanied by cognitive impairment were set as observation subjects, and were divided into a control group and an experimental group using random number table method, with 58 patients in each. The control group received treatment with fluoxetine hydrochloride capsules, while the experimental group was administered Xinyue Decoction Granules in addition to the treatment regimen of the control group. The treatment lasted for 8 weeks for both groups. Comparison was made between the two groups regarding the changes in TCM syndrome scores. Hamilton Depression Scale (HAMD-24) was used to assess the degree of depression, and Montreal Cognitive Assessment (MoCA BJ) was used to assess cognitive ability; the serum levels of brain-derived neurotrophic factor (BDNF), IL-1β, IL-6 and TNF-α were detected by ELISA; the adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate of TCM syndromes was 90.4% (47/52) in the experimental group and 75.5% (40/53) in the control group, with statistical significance ( χ2=4.11, P<0.05); the total effective rate of MoCA-BJ was 76.9% (40/52) in the experimental group and 58.5% (31/53) in the control group, with statistical significance ( χ2=4.61, P<0.05); the total effective rate of HAMD-24 was 88.5% (46/52) in the experimental group and 71.7% (38/53) in the control group, with statistical significance ( χ2=4.07, P<0.05). After treatment, the TCM syndrome score, HAMD-24 and MoCA-BJ scores of the experimental group were lower than those in the control group ( t=-3.51, -5.11, 2.39, P<0.01 or P<0.05); the level of serum BDNF [(10.49±1.76) ng/L vs. (9.61±1.85) ng/L, t=2.28] in the observation group was higher than that of the control group ( P<0.05), and the levels of IL-1β, IL-6 and TNF-α were lower than those in the control group ( t=-2.50, -2.46, -2.18, P<0.05). During the treatment, the incidence of adverse reactions was 5.77% (3/52) in the experimental group and 7.55% (4/53) in the control group, without statistical significance ( χ2=0.13, P>0.05). Conclusion:Xinyue Decoction combined with fluoxetine hydrochloride can reduce the degree of depression in elderly patients with cognitive impairment of depression, improve the cognitive ability of patients and clinical efficacy.

Colorectal cancer has a high incidence and mortality rate,and some patients do not benefit from existing treatments.Intestinal inflammation is one of the major risk factors for colorectal cancer,and an abnormal tumor immune microenvironment plays a crucial role in its occurrence and progression.As a deubiquitinating enzyme,USP11 stabilizes target proteins by removing ubiquitin molecules,thereby exerting dual roles in the antitumor immunity of colorectal cancer.USP11 enhances the specific recognition and cytotoxic function of T cells,promotes the differentiation and regulation of CD4+T cells,and induces macrophage polarization.Investigating the role and regulatory mechanisms of USP11 in colorectal cancer may provide new strategies and targets for its treatment.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy is the primary surgical treatment for lung cancer. A significant factor affecting postoperative recovery is prolonged air leak (PAL). Despite numerous clinical strategies could prevent and manage postoperative PAL, its incidence remains high. Phrenic nerve cryotherapy (PNC) temporarily inhibits phrenic nerve function, causing diaphragm elevation, which reduces thoracic cavity volume, enhances pleural apposition, and mitigates air leakage. This study investigates the efficacy of PNC in preventing postoperative PAL during VATS lobectomy. METHODS: A total of 108 eligible lung cancer patients who underwent surgery at the Department of Thoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, from June 2023 to January 2025, were enrolled and randomly assigned to the control group (n=54) and the experimental group (n=54). The patients in both the two groups received VATS lobectomy and systematic lymph node dissection, with the experimental group also undergoing PNC during the operation. The baseline characteristics, intraoperative, postoperative indicators and dynamic changes in air leakage between the two groups were compared. RESULTS: The baseline clinical characteristics were comparable between the two groups (P>0.05). The incidence of pulmonary air leakage at 24 h after surgery (31.5% vs 29.6%) and the incidence of postoperative PAL (20.4% vs 14.8%) showed no significant differences between the two groups (P>0.05). The intraoperative air leak test to 24 hours after surgery revealed that air leakage ceased in 8 cases (32.0%) in the control group, compared to 14 cases (46.7%) in the experimental group. Moreover, during the progression from air leakage at 24 hours post-surgery to postoperative PAL, air leakage ceased in 6 cases (35.3%) in the control group and 8 cases (50.0%) in the experimental group, with a statistically significant difference (P<0.001). Compared to the control group, the patients in the experimental group exhibited more pronounced postoperative diaphragmatic elevation that recovered to a slightly higher than preoperative level by 3 mon after surgery. CONCLUSIONS The combination of PNC and active lung repair can serve as an important intervention for patients at high risk of intraoperative air leakage, reducing the occurrence of postoperative PAL.
Humans ; Thoracic Surgery, Video-Assisted/adverse effects* ; Male ; Female ; Middle Aged ; Lung Neoplasms/surgery* ; Aged ; Phrenic Nerve/physiopathology* ; Cryotherapy ; Pneumonectomy/adverse effects* ; Postoperative Complications/etiology* ; Adult

Objective:To analyze the efficacy and safety of fascicular unit extraction (FUE) in treatment of bromhidrosis.Methods:A total of 12 patients (24 sides) with bromhidrosis were retrospectively enrolled from the Department of Plastic Surgery, Shanghai East Hospital, Tongji University, from May 2023 to December 2024. The cohort included 5 males and 7 females, aged 17-37 (28.3±6.1) years. All patients underwent FUE treatment. A trephine with an inner diameter of 1.5 mm was used to extract axillary hair and apocrine gland tissues along the direction of hair follicle units, followed by "8-shaped" elastic bandage compression dressing for fixation. The operation time and wound healing time were recorded. The patients were followed up for 6-12 months. The improvement of bromhidrosis was evaluated using the visual analogue scale (VAS), and the adverse reaction incidence was documented.Results:The operation duration of FUE was (1.5±0.3) h, and the wound healing time was (5.2±1.3) d. All patients completed follow-up. Axillae showed no obvious scars or only scattered pinhead-sized pigmentation. The patients′ preoperative VAS was 8 (8, 8) scores, which decreased significantly to 0 (0, 3) scores at the last postoperative follow-up ( P<0.001). Bromhidrosis resolved completely (VAS: 0) in 14 sides (58.3%), and improved (VAS: 2-3) in 10 sides (41.7%), with no recurrence observed. No patients reported significant intraoperative or postoperative pain, subcutaneous hematoma, flap necrosis, infection, paresthesia, or shoulder mobility limitation. One patient developed an epidermoid cyst 2 months postoperatively, resolved after surgical resection. Conclusion:FUE can be used to treat bromhidrosis with high efficacy and low adverse reaction rates.