Objective To explore the correlation between systemic family dynamics characteristics and adolescent depressive symptoms, and the mediating role of negative life events between them. Methods A cross-sectional study was conducted on 124 adolescent patients diagnosed with depressive disorder according to the international classification of diseases (ICD)-10 criteria at the Psychosomatic Medicine Department of Shanghai East Hospital Affiliated to Tongji University from September 2021 to February 2023. The second edition of the Scale of Systematic Family Dynamics (SSFD), Children's Depression Inventory (CDI), and Adolescent Self-Rating Life Events Checklist (ASLEC) were utilized to evaluate the family dynamics characteristics, depressive symptoms, and negative life events. Canonical correlation analysis was performed to explore the relationships between 4 dimensions of SSFD [family atmosphere (FA), individuation (IN), system logic (SL), illness concept (IC)] and 5 factors of CDI (low self-esteem, negative emotion, anhedonia, inefficiency, interpersonal problem). A mediation effect analysis using Bootstrap test was conducted to analyze the mediating role of negative life events between family dynamics and adolescent depressive symptoms. Results The scores for FA, SL, and IN in SSFD were negatively correlated with the total score of CDI (r=-0.359, -0.256, -0.291, P<0.01), and negatively correlated with the total score of ASLEC too (r=-0.318, -0.371, -0.406, P<0.01). However, a positive correlation was observed between the total scores of ASLEC and CDI (r=0.633, P<0.01). Canonical correlation analysis between the 4 dimensions of SSFD and the 5 factors of CDI revealed one pair of statistically significant canonical variables (U₁, V₁) with a canonical correlation coefficient of 0.483 (P<0.05). This indicates that the canonical variable U₁ of SSFD was primarily influenced by FA, while the canonical variable V₁ of CDI was mainly affected by low self-esteem and interpersonal problems. The mediating analysis showed that the effects of FA, IN, and SL scores on CDI total score were all weak (-0.147, -0.117, -0.102, respectively) but statistically significant (P<0.05). The direct effect of IN and SL scores on CDI total score was not statistically significant (P>0.05), while the direct effect of FA score on CDI total score was statistically significant (-0.076, P<0.05). Additionally, the mediating effect of ASLEC between the scores of FA, IN, SL and CDI total score were all significant (-0.071, -0.095, -0.087, respectively) (P<0.05). Conclusions Adolescent depressive symptoms may be influenced by systemic family dynamics characteristics and negative life events. Negative life events mediate the influence of FA, IN, and SL on depressive symptoms. However, the IC is not related to depressive symptoms in adolescents.

Objective To investigate the improvement effect of 18kD translocator protein (TSPO) ligand YL-IPA08 on lipopolysaccharide (LPS)-induced depressive, anxiety-like behaviors and cognitive dysfunction in mice and the related anti-inflammatory mechanism. Methods (1) 50 male C57BL/6J mice were randomly divided into control group, LPS model group, LPS+YL-IPA08 (1.0 or 3.0 mg/kg) group and YL-IPA08 (3.0 mg/kg) group, with 10 mice in each group. Mice in LPS model group were intraperitoneally injected with LPS (0.5 mg/kg) once on day 1 and day 8. Mice in LPS+YL-IPA08 (1 or 3 mg/kg) and YL-IPA08 (3.0 mg/kg) groups were intragastrically administered YL-IPA08 (1.0 or 3.0 mg/kg) for 13 consecutive days, once a day. From the 9th to 12th day, the open field test, tail suspension test, forced swimming test, novel object recognition test and elevated-plus maze test were used to evaluate the depressive, anxiety-like behaviors and cognitive function of mice. Western blotting was used to detect the expression levels of postsynaptic density protein 95 (PSD95) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of mice. (2) BV2 mouse microglia cells were divided into control group (phosphate buffered saline incubation for 1 h), LPS model group (incubated with 1.0 mg/L LPS for 6 h), LPS+YL-IPA08 (0.5 or 1.0 μmol/L) group (incubated with 0.5 or 1.0 μmol/L YL-IPA08 for 1 h and then incubated with 1 mg/L LPS for 6 h), and YL-IPA08 group (incubated with 1.0 μmol/L YL-IPA08 for 1 h). ELISA was used to detect the expression levels of inflammatory factors interleukin-1β (IL-1β), interferon-γ (IFN-γ), IL-4, IL-10 and transforming growth factor-β₁ (TGF-β₁). Western blotting was used to detect the expression levels of the members of Smad protein family (Smad2, Smad3) mediating signal transduction of TGF-β. Results (1) The results of behavioral experiments showed that there was no significant difference in the total movement distance of mice in each group in the open field test (P>0.05). Compared with the control group, the number of entries and duration time in the central area of mice in LPS model group were significantly decreased (P<0.05); the immobility time in the tail suspension test and the forced swimming test was significantly prolonged (P<0.05); the recognition index in the novel object recognition test, the percentage of entries into the open arms and the percentage of duration time in the open arm in the elevated-plus maze test were significantly decreased (P<0.05), and the expression levels of PSD95 and BDNF in the prefrontal cortex were significantly decreased (P<0.05). Compared with LPS model group, above behavioral and expression changes in LPS+YL-IPA08 (3.0 mg/kg) group were significantly reversed (P<0.05). (2) Compared with control group, the expression levels of pro-inflammatory factors IL-1β and IFN‑γ in BV2 cells in LPS model group were significantly increased (P<0.05), and the expressions of anti-inflammatory factors IL-4, IL-10 and TGF-β₁ were significantly decreased (P<0.05), and the expression levels of Smad2 and Smad3 were significantly decreased (P<0.05). Compared with LPS model group, the expression level of IFN-γ in BV2 cells in LPS+YL-IPA08 (0.5 μmol/L) group was significantly decreased, and the expression levels of IL-4 and TGF-β₁ were significantly increased (P<0.05); the above changes were significantly reversed in LPS+YL-IPA08 (1.0 μmol/L) group (P<0.05). Conclusion YL-IPA08 can significantly attenuate LPS-induced depressive and anxiety-like behaviors in mice and alleviate the decline in cognitive dysfunction, which mechanism may be related to improving neuroinflammation and regulating the TGF-β/Smad pathway.

Objective To explore the value of constructing a model to predict the number of positive cores in systematic biopsy in prostate cancer (PCa) using a combination of radiomics features based on magnetic resonance imaging and clinical indicators. Methods Retrospectively collected magnetic resonance imaging and clinical data from two medical institutions (Gansu Provincial Hospital from January 2018 to February 2023, Zhangye People's Hospital Affiliated to Hexi College from April 2020 to February 2023). The 155 patients from Gansu Provincial Hospital were randomly divided into a training set (n=109; 80 cases with positive needle count ≥6 and 29 cases with positive needle count <6) and an internal validation set (n=46; 34 cases with positive needle count ≥6 and 12 cases with positive needle count <6) in a 7:3 ratio. The 43 patients from Zhangye People's Hospital Affiliated to Hexi College were used as external validation set. Small field of view high-resolution T₂-weighted imaging (sFOV HR-T₂WI) and contrast-enhanced delayed-phase images were selected to extract radiomic features from the three-dimensional region of interest of the entire prostate, and radiomics model was constructed and Radscores calculated after dimensionality reduction and feature selection. Univariate and multivariate logistic regressions were used to screen for independent risk factors for positive cores in systematic biopsy. Nomogram was constructed using Radscore and clinical independent risk factors to predict the number of positive cores in systematic biopsy in PCa patients, which was then externally validated. Results Age, alkaline phosphatase (ALP), free prostate specific antigen (FPSA), total prostate specific antigen (TPSA), FPSA/TPSA ratio, and prostate specific antigen density (PSAD) were not statistically significantly different between the training, internal validation, and external validation sets (P>0.05). FPSA, TPSA, FPSA/TPSA ratio, and PSAD were significantly different between the positive cores <6 and positive cores ≥6 groups (P<0.001). Univariate logistic regression analysis showed that FPSA (P<0.001), TPSA (P<0.001), FPSA/TPSA ratio (P=0.001), PSAD (P<0.001), and Radscore (P<0.001) were risk factors for positive cores in systematic biopsy in PCa. Multivariate logistic regression analysis showed that PSAD (OR=0.251, 95%CI 0.063-0.996, P=0.049) and Radscore (OR=1.990, 95%CI 1.409-2.812, P<0.001) were independent risk factors for positive cores in systematic biopsy in PCa. The clinical models achieved AUCs of 0.849(95%CI 0.774-0.924), 0.817(95%CI 0.693-0.941), and 0.631(95%CI 0.439-0.822); the 12 features for radiomics models are derived solely from sFOV HR-T₂WI, the radiomics models achieved AUCs of 0.868(95%CI 0.791-0.945), 0.846(95%CI 0.695-0.996), and 0.815(95%CI 0.660-0.970); the nomogram achieved AUCs of 0.921(95%CI 0.869-0.973), 0.868(95%CI 0.743-0.992), and 0.840(95%CI 0.702-0.978) in the training set, internal validation set, and external validation set, respectively. Conclusions The combination of radiomic features extracted from sFOV HR-T₂WI and PSAD can preoperatively be used as a noninvasive manner to predict the number of positive cores of the PCa patients. This approach has a certain value in risk stratification of PCa patients and guiding personalized clinical management.

Objective To explore the regulatory role of transient receptor potential channel 6(TRPC6) on podocyte autophagy under the influence of homocysteine (Hcy) in mouse kidney. Methods Mouse renal podocytes were divided into control group and Hcy groups (stimulated by Hcy at 40, 60, 80 and 100 μmol/L for 48 h). The level of TRPC6 mRNA was assessed using quantitative reverse transcription polymerase chain reaction (qRT⁃PCR) to identify the optimal Hcy concentration for subsequent experiments. Western blotting was employed to evaluate the expression levels of autophagy-related proteins LC3 Ⅱ and p62, as well as the expression levels of podocyte structural proteins Nephrin and Podocin. The expression levels of TRPC6 mRNA and protein in both groups were determined using qRT-PCR, Western blotting and immunofluorescence. Transfections of cells with TRPC6 overexpression or interference were set as follows: (1) control group (untreated), negative control group of TRPC6 overexpression, and TRPC6 overexpression group; (2) control group (untreated), negative control group of TRPC6 interference, and TRPC6 interference group (si-1, si-2, si-3).The expression level of TRPC6 was detected using qRT⁃PCR. The cells after overexpressing or interfering of TRPC6 were further set as follows: (1) control group (untreated), Hcy group (80 μmol/L Hcy added), TRPC6 overexpression control+Hcy group, TRPC6 overexpression+Hcy group; (2) control group (untreated), Hcy group, TRPC6 interference control+Hcy group, and TRPC6 interference+Hcy group. The expression levels of p62, LC3 Ⅱ, and TRPC6 proteins were detected using Western blotting. Results qRT⁃PCR detection results showed that compared with control group, the expression level of TRPC6 mRNA in Hcy group increased with the increase of Hcy concentration, with the highest expression level observed at 80 μmol/L Hcy. Therefore, 80 μmol/L Hcy was selected as the optimal concentration for intervention. At this time, the expression level of autophagy-related protein LC3 Ⅱ increased, and the expression level of p62 decreased (P<0.05). Western blotting results showed that compared with control group, the expression levels of podocyte-related proteins Nephrin and Podocin in Hcy group were significantly decreased (P<0.05). qRT⁃PCR results showed that compared with control group, the expression level of TRPC6 mRNA in Hcy group was significantly increased (P<0.05). Compared with negative control group for TRPC6 overexpression, both mRNA and protein expression levels of TRPC6 in TRPC6 overexpression group were significantly higher (P<0.05). Compared with negative control group for TRPC6 interference, both mRNA and protein expression levels of TRPC6 in TRPC6 interference group were significantly decreased (P<0.05). Western blotting results showed that compared with negative control group for TRPC6 overexpression, the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 overexpression+Hcy group was significantly increased, and the expression level of p62 was significantly decreased (P<0.05). Compared with TRPC6 negative control+Hcy group for TRPC6 interference+Hcy, the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 interference+Hcy group was significantly decreased, and the expression level of p62 was significantly increased (P<0.05). Conclusion Hcy can induce autophagy of renal podocytes. Inhibiting the expression of TRPC6 can significantly reduce the autophagy damage to podocytes.

Trastuzumab deruxtecan (T-DXd) is a new generation of antibody-drug conjugate targeting human epidermal growth factor receptor 2. It has strong antitumor effects and has been recommended by many authoritative guidelines at home and abroad. Drug-induced interstitial lung disease (DILD) is one of the common adverse reactions and causes of death of T-DXd and is an important factor limiting its clinical application. The pathogenesis of DILD induced by T-DXd is still unclear, and the mainstream view holds that it may be related to the non-target-dependent uptake of the drug. Glucocorticoids are an important treatment method for DILD, and other alternative drugs still lack clinical effectiveness evidence. The research progress on the pathogenesis of T-DXd induced DILD was summarized in this review, aiming to provide new ideas for the prevention and treatment of DILD.

Objective To investigate the viability of Runt-related transcription factor 1 (RUNX1) as a biomarker for gastric cancer and to assess the impact of the small molecule inhibitor Ro24-7429 on the proliferation, migration, and invasion of gastric cancer cells following targeted modulation. Methods Through the GEPIA database, we analyzed RUNX1 mRNA expression in gastric cancer or normal gastric tissues. Utilizing RUNX1 expression data from the TCGA database, a receiver operating characteristic (ROC) curve was constructed to appraise the potential of RUNX1 as a gastric cancer biomarker. In September 2022, we collected tissue samples from 6 patients with gastric cancer from the Department of General Surgery at the Second Hospital of Lanzhou University. After extracting tissue proteins, Western blotting was employed to compare RUNX1 protein expression in tumor and adjacent tissues. Gastric cancer cell lines with high RUNX1 expression were identified and the suppressive effect of the small molecule inhibitor Ro24-7429 on RUNX1 protein expression was verified by Western blotting. the effect of Ro24-7429 was validated by using CCK-8, colony formation, cell scratch, and Transwell assays. RUNX1 protein levels in gastric cancer tissues were quantified using immunohistochemical staining. An organoid model of gastric cancer was then established from the high-expression samples and verified by both HE and immunization analyses. Lastly, the impact of Ro24-7429 on the growth of gastric cancer organoids with meticulous tracking was evaluated using a biological microscope within a designated area. Results The analysis from the GEPIA database revealed a heightened expression of RUNX1 mRNA in gastric cancer tissues compared with normal tissues (P<0.05). The ROC curve derived from the RUNX1 expression data in the TCGA database boasts an area under the curve (AUC) of 0.956, underscoring RUNX1's potential as a robust diagnostic marker. Western blotting results revealed significantly higher RUNX1 protein expression in gastric cancer tissues than in adjacent tissues (P<0.001). Among 5 gastric cancer cell lines studied, AGS and HGC27 exhibited pronounced RUNX1 protein expression (P<0.001). The small molecule inhibitor Ro24-7429, targeting RUNX1, potently suppressed RUNX1 expression in gastric cancer cells. The results from CCK-8, colony formation, scratch, and Transwell assays showed that Ro24-7429 effectively inhibited proliferation, migration, and invasion of gastric cancer cells (P<0.001). In a gastric cancer organoid model derived from high RUNX1 expression samples, the RUNX1 expression was remarkably consistent with its originating tissue. As expected, upon the targeted inhibition of RUNX1 using Ro24-7429, the cancer organoids significantly reduced growth capacity. Conclusions RUNX1 shows potential as a biomarker for gastric cancer. Ro24-7429 specifically inhibits RUNX1 expression and suppresses tumor cell proliferation, migration, and invasion in gastric cancer cell lines and organoid models.

Objective To investigate the correlation between DNA methyltransferase 3a (DNMT3a) expression and prognosis of lung squamous cell carcinoma (LSCC), as well as to elucidate the potential molecular mechanisms of DNMT3a in LSCC progression. Methods A retrospective analysis was conducted on a cohort of 47 LSCC patients who underwent surgery in the Department of Thoracic Surgery, the Second Affiliated Hospital of Air Force Medical University between May 2009 and January 2014. DNMT3a expression in LSCC tissues and paired adjacent non-cancerous tissues was assessed using immunohistochemical (IHC) staining. Patients were categorized into two groups based on the median IHC score of DNMT3a in LSCC tissues: high DNMT3a expression group (n=25) and low DNMT3a expression group (n=22). Prognostic correlation was analyzed in combination with clinicopathological data and public biological databases. To explore the molecular mechanisms of DNMT3a in LSCC progression, H1703 LSCC cell lines with overexpressed DNMT3a were established using a lentiviral infection method, with the creation of DNMT3a overexpression group and control group. Functional phenotype experiments were then conducted to test the differences in cell proliferation and migration between the two groups. DNMT3a overexpression tumor xenograft models were also established in nude mice, with the creation of DNMT3a overexpression group and control group (3 mice per group), to observe the growth of subcutaneous xenograft tumors. Western blotting analysis was employed to detect the expression of related proteins in the two groups of cells and subcutaneous xenograft tumors. Functional rescue experiments involved treating DNMT3a overexpression cells with c-Myc inhibitor (10058-F4) and assessing cell proliferation using EdU proliferation staining. Subsequently, DNMT3a overexpression cells were infected with RNAi-Zinc finger E-box binding homeobox 1 (ZEB1) lentivirus to knock down ZEB1 expression, and a Transwell migration assay was utilized to detect cell migration. Finally, DNMT3a overexpression group and control group were treated with DNMT specific inhibitor (SGI-1027), and the effects of DNMT3a inhibition on cell proliferation and migration were observed in both overexpression and control groups. Results IHC analysis revealed significantly higher DNMT3a level in LSCC tissues compared to adjacent non-cancerous tissues (P<0.0001). High DNMT3a expression was closely associated with N stage, clinical stage and tumor differentiation degree (P<0.05 or P<0.01), and it was identified as an independent risk factor for poor prognosis in LSCC patients (P<0.05). Functional phenotype experiments indicated that DNMT3a overexpression group exhibited significantly higher colony formation number, proportion of EdU-positive cells, wound healing migration rate, and Transwell cell migration number compared with control group (P<0.05). The volume and weight of subcutaneous xenograft tumors in DNMT3a overexpression group were significantly higher than those in control group (P<0.001). Western blotting showed that the protein expression levels of c-Myc and ZEB1 in DNMT3a overexpression group were significantly higher than those in control group. Functional rescue experiments demonstrated a significant reduction in the proportion of EdU-positive cells after 10058-F4 treatment in DNMT3a overexpression group (P<0.05). Knockdown of ZEB1 led to a significant decrease in the number of Transwell cell migration in DNMT3a overexpression group (P<0.05), with no significant change in DNMT3a protein expression. Additionally, inhibition of DNMT3a with SGI-1027 resulted in a significant decrease in colony formation number and migration rate in both DNMT3a overexpression group and control group (P<0.05). Conclusions High expression of DNMT3a is a significant independent risk factor for poor prognosis of LSCC patients. DNMT3a is likely to promote the proliferation of LSCC by upregulating c-Myc expression and to enhance the migration of LSCC by increasing ZEB1 expression.

Objective To investigate the characteristics of coagulation function changes in patients with exertional heat illness (EHI) at different core temperatures(Tc). Methods A retrospective analysis was conducted on the clinical data of 346 EHI patients admitted to the emergency or intensive care units of 24 military hospitals from March 2021 to November 2022. According to the Tc at admission, patients were divided into 4 groups: Tc <39 ℃ group (n=223), 39 ℃ ≤Tc <40 ℃ group (n=60), 40 ℃ ≤Tc <41 ℃ group (n=35), 41 ℃ ≤Tc <42 ℃ group (n=17), and Tc ≥42 ℃ group (n=11). Based on the occurrence of heat stroke, the 346 EHI patients were further divided into heat stroke group (n=63) and non-heat stroke group (n=283). Basic information, complete blood count, coagulation function, liver and kidney function, and other laboratory indicators of the patients in each group were collected and statistically analyzed. Multifactorial logistic regression analysis was used to identify independent risk factors for the development of heat stroke in EHI patients. The diagnostic value of prothrombin time (PT), D-dimer, and platelet count for EHI patients developing heat stroke was assessed using the receiver operating characteristic (ROC) curve. Results When Tc exceeded 39 ℃, D-dimer levels in EHI patients increased significantly and further elevated with rising Tc (P<0.05). When Tc exceeded 40 ℃, platelet count and fibrinogen levels decreased, and PT was prolonged (P<0.05). When Tc exceeded 41 ℃, activated partial thromboplastin time (APTT) was significantly prolonged, and platelet count and fibrinogen level decreased (P<0.05). Multivariate logistics regression analysis showed that PT (OR=1.120, 95%CI 1.015-1.236), D-dimer (OR=1.322, 95%CI 1.129-1.549), and platelet count (OR=0.991, 95%CI 0.985-0.997) were independent risk factors for heat stroke (P<0.05). The area under the ROC curve (AUC) for D-dimer in diagnosing heat stroke was 0.796 (95%CI 0.732-0.860, P<0.001) with sensitivity and specificity of 69% and 80%, respectively, when D-dimer was greater than 0.9 μg/ml. The AUC for PT in diagnosing heat stroke was 0.708 (95%CI 0.628-0.788, P<0.001), with sensitivity and specificity of 42% and 97%, respectively, when PT was greater than 16.4 s. The AUC for platelet count in diagnosing heat stroke was 0.724 (95%CI 0.642-0.807, P<0.001), with the sensitivity and specificity of 52% and 94%, respectively, when the platelet count was less than 140×10⁹/L. Conclusions The degree of Tc elevation in EHI patients is positively correlated with the severity of coagulation dysfunction. Prolonged PT, increased D-dimer level, and decreased platelet count are independent risk factors for the development of exertional heat stroke in EHI patients.

Objective To investigate the accuracy and clinical efficacy of 3D-printed patient-specific instruments (PSIs) in medial open-wedge high tibial osteotomy (MOWHTO) for the treatment of knee varus deformity and medial compartment osteoarthritis. Methods Clinical data of 69 patients with knee varus deformity and medial compartment ostecarthritis who underwent MOWHTO treatment in Department of Orthopedics, Fuyang People's Hospital Affiliated to Anhui Medical University from October 2017 to March 2021 were retrospectively analyzed. Patients were divided into two groups: 3D group using 3D-printed PSIs (n=37) and conventional group using standard procedures (n=32). The lateral hinge point error, medial osteotomy point error, osteotomy surface angle error, osteotomy depth error, intraoperative distraction angle, femoral tibial angle (FTA), proximal tibial medial angle (MPTA), knee rotation angle (KRA), posterior tibial slope (PTS), intraoperative weight-bearing line ratio (WBLR), and the last follow-up International Knee Documentation Committee (IKDC) score of the two groups were compared. The correlation between accuracy indicators and curative effect was analyzed using Spearman's rank correlation. Results The follow-up time for the 3D group was 19-26 months, averaging (21.1±3.6) months; for the conventional group, it was 14-26 months, averaging (23.6±1.6) months. No significant differences were found between the two groups in lateral hinge point error, osteotomy depth error, intraoperative distraction angle, and the FTA, MPTA, KRA, PTS, IKDC score at the last follow-up (P>0.05). However, the 3D group showed significantly lower errors in medial osteotomy point, osteotomy surface angle, and intraoperative WBLR compared with conventional group (P<0.05). Spearman analysis revealed no correlation between IKDC score and aforementioned accuracy indicators (lateral hinge point error, medial osteotomy point error, osteotomy surface angle error, osteotomy depth error, intraoperative distraction angle, and WBLR) at the last follow-up (P>0.05). Conclusions The use of 3D-printed PSIs in MOWHTO offers a more precise advantage in certain positioning parameters, yet there are still deficiencies in determining WBLR. Compared to traditional MOWHTO surgery, the short-term outcome does not show any significant improvement.

Cerebral small vessel disease (CSVD) is a group of local brain tissue lesions caused by abnormal small vessels in the brain due to different etiologies. The pathogenesis of CSVD is not yet fully understood, and its diagnosis currently mainly relies on clinical imaging examinations. Endothelial cells (ECs) in cerebral blood vessels can play an important role in maintaining the structure and function of the blood-brain barrier, regulating cerebral blood flow, and mediating neurovascular coupling. In recent years, studies have shown that ECs dysfunction plays an important triggering and mediating role in the pathological changes of CSVD, and may even be a key initiating link in its pathogenesis. Moreover, biomarkers related to ECs dysfunction are associated with the severity of CSVD. The review summarizes the role of ECs dysfunction in the pathogenesis of CSVD, and the research progress of related biomarkers, aiming to provide references for the diagnosis and treatment of CSVD.