Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Objective To establish normal reference values for left ventricular trabecular and papillary muscle mass(TPMM)in Chinese adults using MRI and to explore its impact factors.Methods A total of 168 healthy Chinese adults were retrospectively included,and compacted and total left ventricular myocardial mass(LVM)were measured using traditional and dedicated methods,respectively.TPMM was calculated from the difference between total and compacted LVM.Independent sample t-tests and analysis of variance were used to explore the differences in TPMM among genders and age groups,while multiple linear regression was used to explore the independent correlation between TPMM and age,gender,heart rate,systolic blood pressure(SBP),fasting blood glucose(FBG),and body mass index(BMI).Results TPMM for men was significantly larger than that for female(P<0.001).TPMM in the elderly group was significantly larger in female(P<0.05),but not in men.Multiple linear regression showed that BMI and SBP were both independently positively correlated with TPMM,and female and heart rate were independently negatively correlated with TPMM(P<0.05).Conclusion This study provides age-and gender-specific normal reference values for TPMM in Chinese adults.Gender,heart rate,BMI,and SBP are all independently associated with TPMM.

Objective:To investigate the clinical efficacy of Huoxue Quban Decoction combined with Xiyu chloasma patch in the treatment of chloasma.Methods:Randomized controlled trial. A total of 126 chloasma patients were selected and divided into two groups according to the random number table method, 63 in each group. The control group were treated with Xiyu chloasma patch, and the observation group received Huoxue Quban Decoction combined with Xiyu chloasma patch. Both groups were treated continuously for 12 weeks. TCM syndrome scores were performed before and after treatment, and the severity of skin lesions was evaluated by the Melasma Area and Severity Index (MASI). Quality of life was evaluated by the Melasma Quality of Life (MELASQOL) scale. Serum SOD levels were measured by enzyme rate method, MDA levels were measured by micro method, and GSH-Px levels were measured by colorimetric method. Adverse reactions during treatment were recorded and clinical efficacy was evaluatedResults:The total effective rate of the observation group was 90.48% (57/63), while the control group was 71.43% (45/63). The difference between the two groups was statistically significant ( χ2=7.41, P=0.006). After treatment, the scores of traditional Chinese medicine syndrome scores ( Z=8.13), MASI ( Z=8.92), and MELASQOL ( t=11.52) in the observation group were significantly lower than those in the control group ( P<0.01). After treatment, the serum SOD [(203.07±25.24) g/L vs. (176.24±33.98) g/L, t=5.03] and GSH-Px [(8.28±1.27) U/L vs. (7.33±1.28) U/L, t=4.18] levels in the observation group were significantly higher than those in the control group ( P<0.01); MDA[(3.36±1.17) μmol/L vs. (5.20 ± 1.23) μmol/L, t=8.62] was significantly lower than that of the control group ( P<0.01). No significant adverse reactions occurred during the treatment period in both groups. Conclusion:The Huoxue Quban Decoction combined with Xiyu chloasma patch can improve the color, area and quality of life of chloasma lesions and reduce oxidative stress with high safety.

Background/Aims: Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms. Methods: The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs. Results: S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCAmediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK). Conclusions TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis.

Osteochondral lesions of the talus (OLT) frequently manifest following ankle joint trauma, causing ankle pain, swelling and impaired mobility, thereby significantly impeding daily activities of the patients. Presently, clinical treatment approaches encompass both conservative management and surgical intervention. Conservative management endeavors to alleviate symptoms, while patients experiencing persistent symptoms resort to surgical intervention. Commonly employed surgical treatments encompass bone marrow stimulation, autologous osteochondral transplantation, and allogeneic osteochondral transplantation. Bone marrow stimulation is employed as a therapeutic approach for the management of smaller OLT, demonstrating favorable short-term effectiveness; however, the long-term prognosis remains uncertain. Autologous osteochondral transplantation is a viable option for larger OLT lesions, albeit it carries the potential of complications at the donor site. Conversely, allogenic osteochondral transplantation exhibits a diminished success rate. In recent times, the utilization of cell transplantation techniques has garnered escalating interest in the treatment of OLT due to their capacity to regenerate cartilage resembling hyaline and their diverse range of cellular origins. The authors reviewed the progress of cell transplantation in the treatment of OLT, providing a reference for the clinical treatment.

Objective:To compare the efficacies of arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement in the treatment of chronic lateral ankle instability (CLAI) concomitant with fibular tendinitis.Methods:A retrospective cohort analysis was conducted on the clinical data of 31 patients with CLAI concomitant with fibular tendinitis, who were treated in Beijing Tongren Hospital, Capital Medical University between March 2019 and December 2021. The patients included 17 males and 14 females, aged 16-57 years [(32.8±9.6)years]. The anterior drawer test and talar tilt test were positive in all patients preoperatively. Diagnosis was confirmed by physical examination and MRI, and calcaneofibular ligament rupture was excluded. Eleven patients received arthroscopic modified Brostr?m procedure combined with peroneal tendon debridement (modified Brostr?m procedure+tendon debridement group), and 20 underwent pure arthroscopic modified Brostr?m procedure (modified Brostr?m procedure group). The operation time, intraoperative blood loss and length of hospital stay were documented. The visual analogue score (VAS) in peroneal tendon area was assessed before operation and at postoperative 2, 6 and 12 weeks. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and foot and ankle outcome score (FAOS) were assessed before operation and at postoperative 6 and 12 weeks. The anterior drawer test was performed at the last follow-up. The foot and ankle ability measure (FAAM) score was assessed before operation and at the last follow-up. Postoperative wound healing and complications were also observed.Results:All the patients were followed up for 4-19 months [(11.3±3.5)months]. The operation time was (66.0±4.2)minutes in the modified Brostr?m procedure+tendon debridement group, which was significantly longer than (61.5±3.4)minutes in the modified Brostr?m procedure group ( P<0.05). There was no significant difference in intraoperative blood loss or length of hospital stay between the two groups (all P>0.05). Compared with the preoperation, the value of VAS was significantly lowered, and the values of AOFAS ankle-hindfoot score, FAOS and FAAM score were significantly increased at different postoperative timepoints (all P<0.01). No significant differences in the values of VAS, AOFAS ankle-hindfoot score, FAOS or FAAM score were seen between the two groups before operation (all P>0.05). The value of VAS was 3.0(3.0, 4.0) points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 4.0(4.0, 4.0)points in the modified Brostr?m procedure group at 2 weeks postoperatively ( P<0.05). The value of VAS was 2.0(1.0, 3.0)points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 3.0(2.3, 3.0)points in the modified Brostr?m procedure group at 6 weeks postoperatively ( P<0.05). At 12 weeks postoperatively, there was no significant difference in the value of VAS between the two groups ( P>0.05). There were no significant differences in the values of AOFAS ankle-hindfoot score and FAOS between the two groups at 6 or 12 weeks postoperatively (all P>0.05). The anterior drawer test was negative in all patients at the last follow-up. No significant difference was seen in the value of FAAM score between the two groups at the last follow-up ( P>0.05). All incisions were healed well in the first stage after operation, without the occurrence of joint infection, impaired joint motion, nerve injury or deep vein thrombosis. Conclusions:Arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement can both improve the foot function in CLAI patients concomitant with fibular tendinitis. However, the combined treatment allows for early pain relief, without increasing the risk of complications, and can therefore contribute to a faster postoperative recovery.

Objective To explore the effectiveness of the Five Elements Music Therapy(FEMT)in relieving stress in participants with different cultural backgrounds,and to compare the differences between the FEMT and the Western Art Music Therapy(WAMT)in stress relief.Methods This was a comparative pilot randomized pre-post repeated measures study,37 subjects were allocated with 2 dropped out,with an inclusion-ended sample of 35 subjects,23 from Canada and 12 from China.After informed consent,all subjects were randomly assigned to listening to either Five Elements Music or Western Art Music at home for 30 minutes,twice a week for four weeks.Participants were asked to use headphones,measure their pulse rate before and after each session,and fill out five questionnaires,including a background and demographic survey(reporting age,gender,education,cultural background,listening experience).Self-assessment of stress(pre-post after each session),General Hospital Anxiety/Depression Scale(HADS,weekly after 2nd session),Perceived Stress Survey(PSS,weekly after 2nd session),the Music Therapy Intervention Survey(MTIS,pre-post each session).Results ①There was a significant decrease in self-assessed stress scores after the second session in the FEMT compared with the WAMT group(t=-2.057,P=0.046).②In both groups,there was a significant decrease in stress scores pre-post treatment in each group(WAMT t=5.026;FEMT T=7.645,P=0.000).③There was no significant difference between the two groups in post-intervention HADS scores(P>0.05);In the Chinese sample,there was a significant difference in HADS scores after the eighth session in both FEMT and WAMT groups(t=-3.862,P=0.003),and a statistically significant difference in HADS pre-post intervention in the FEMT((t=5.117,P=0.004).There was a significant difference in MTIS pre-post treatment in the WAMT(t=-2.572,P=0.023),but in not the FEMT group(t= 1.331,P=0.207).Conclusion This pilot trial explores a safe and feasible self-administered music therapy approach for stress in two distinct cultural groups,and for the first time provides preliminary comparison and evidence of effectiveness of FEMT and WAMT in alleviating stress and anxiety.Further investigation with bigger randomized samples is needed to elucidate the effects of different kinds of music and cultural groups on stress and anxiety levels.

Objective:To investigate the changes of T1 and T2 values in residual liver after major liver resection in rats and the relationship with pathologic indices related to liver regeneration.Methods:Seventy healthy male Sprague Dawley rats, SPF grade, aged 7-8 weeks, weighting 250-280 g, were divided into MR scan group ( n=14) and pathologic analysis group ( n=56). The MR scan group was further divided into partial hepatectomy group ( n=7) and the sham operation group ( n=7). MRI T 1 mapping and T 2 mapping were performed before surgery and on day 1, 2, 3, 5, 7, 14, 21 after surgery. T1 and T2 values of liver parenchyma were measured. In the pathologic analysis group, 7 rats were randomly included at each time point before and after surgery for pathologic examination, the diameter and proliferative activity (Ki-67 indices) of hepatocytes were assessed. The changes of imaging and pathologic indices were observed, and the correlations between MR parameters and liver volume and pathologic indices were analyzed. Results:Both T1 and T2 values in liver parenchyma were increased on day 1 after surgery and reached their maximum values on day 2 ( P=0.005 and P<0.001, compared with baseline), then were gradually decreased, and recovered to the preoperative level on day 14 and 21 ( P>0.05), respectively. T2 value was correlated with hepatocyte diameter, liver volume and Ki-67 indices better ( r=0.640, -0.764, 0.765, respectively, all P<0.001). T1 value was correlated with hepatocyte diameter, liver volume and Ki-67 indices ( r=0.472, -0.481 and 0.444, all P<0.001). Conclusion:The T1 and T2 values of rats liver remnant parenchyma showed regular changes, and were correlated with liver regeneration indices, which reflect the microscopic changes of rat liver remnant parenchyma, and are expected to be used for quantitative monitoring of liver remnant regeneration.

Objective:To compare the value of difference between thromboelastogram (TEG), coagulation function and mean platelet volume (MPV)/platelet count (PLT) ratio in sepsis patients with short-term prognosis.Methods:A total of 271 patients with sepsis admitted to the Affiliated Hospital of Xuzhou Medical University from January 2020 to September 2021 were retrospectively analyzed. The clinical data of the patients were recorded, and the SOFA score and APACHE Ⅱ score were calculated. The patients were followed up within 28 days and were divided into the survival group and death group. The TEG, coagulation function and MPV/PLT ratio were compared between the two groups. The independent prognostic factors of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio were confirmed by Logistic regression analysis. The combination of Angle + CI + AT-Ⅲ + D-Di +MPV/PLT ratio was established, and the ROC curve was drawn to evaluate the prognostic value of Angle, CI, AT-Ⅲ and D-Di combined with MPV/PLT ratio in patients with sepsis.Results:The mortality rate of patients with sepsis was 42.4%. The D-Di and MPV/PLT ratio of the death group were significantly higher than those of the survival group, and the differences were statistically significant. Angle, CI and AT-III in the death group were significantly lower than those in the survival group, and the differences were statistically significant. Logistic regression analysis showed that Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio were independent predictors of the prognosis of patients with sepsis (all P < 0.05) . The area under the curve of the combined detection of Angle, CI, AT-Ⅲ, D-DI and MPV/PLT ratio to evaluate the prognosis of sepsis at 28 days was 0.931, which was larger than that of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio alone (0.755, 0.790, 0.776, 0.729 and 0.746). The sensitivity and specificity of the combination of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio were 83.5% and 91.0%, which were also higher than those of the single index . Conclusions:Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio are independent prognostic predictors of patients with sepsis. The combination of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio has high sensitivity and specificity in evaluating the prognosis of sepsis.

Objective:To evaluate the value of implementing strict aseptic operation procedures in preventing central venous catheter-related infections.Methods:This retrospective cohort study consisting of non-surgical patients who underwent central venous catheterization from 2015 to 2019 were conducted.The patients were divided into 2 groups according to routine aseptic procedures and strict aseptic procedures, the patients between 2015 and 2017 served as routine aseptic procedure group (group C), and the patients between 2017 and 2019 served as strict aseptic procedure group (group E ). The occurrence of central venous catheter-related infections (local infection, bloodstream infection) was recorded within 6 days after catheterization.Results:Compared with group C, the incidence of central venous catheter-related local infection was significantly decreased (1.79% vs. 0.48%, P<0.001; the rate ratio being 0.27 ranged in 0.10-0.30), while no significant change was found in the incidence of central venous catheter-related bloodstream infection in group E (0.29% vs. 0.19%, P>0.05). The cumulative incidence of central venous catheter-related infections was 0.67%(<1.00%) in group E. Conclusions:Implementation of strict aseptic procedures during central venous catheterization can further reduce the occurrence of central venous catheter-related infections, which has significant clinical value.