OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues（MCACs） and investigate the activities of them against breast cancer. METHODS The analogues F1， F2， and F3 were obtained by aldol condensation reaction， and their antitumor activities（including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549） were detected by MTT assay [evaluated with half inhibitory concentration（IC50）]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1， F2 and F3 acting on breast cancer， and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high， medium and low concentrations （16， 8， 4 μmol/L） of F1， F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1， F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin， IC50 of analogues F1， F2 and F3 to A549 and MCF-7 cells（except for IC50 of analogue F2 to A549 cells） were decreased significantly（P＜ 0.05 or P＜0.01）； among them， IC50 of analogue F2 to MCF-7 cell was the lowest， being（9.67±1.27） μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1， F2 and F3 with the first core target epidermal growth factor receptor （EGFR）， protein kinase B （AKT） and AKT were 5.909 2， 8.402 5 and 6.486 6， respectively； high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells（P＜0.01）， while low， medium， and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells（P＜0.05 or P＜0.01）. Medium concentration of F1， F2， and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells（P＜0.01）. CONCLUSIONS Designed and synthesized MCACs F1， F2 and F3 all have good anti- breast cancer activity， and F2 has better anti-breast cancer activity.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

This study aims to investigate the therapeutic efficacy of 50 Hz-0.6 mT low-frequency pulsed electromagnetic field (PEMF) on postmenopausal osteoporosis in ovariectomized rats. Thirty 3-month-old female SD rats were selected and divided into a sham operation group (Sham), an ovariectomized model group (OVX), and a low-frequency pulsed electromagnetic field (PEMF) treatment group, with 10 rats in each group. After 8 weeks, the whole-body bone mineral density (BMD) of each group of rats was measured. The treatment group began to receive PEMF stimulation for 90 minutes daily, while the OVX group only received a simulated placement without electricity. After 6 weeks of intervention, all rats were sacrificed and tested for in vitro BMD, micro-CT, biomechanics, serum biochemical indicators, and bone tissue-related proteins. The results showed that the BMD of the OVX group was significantly lower than that of the Sham group 8 weeks after surgery, indicating successful modeling. After 6 weeks of treatment, compared with the OVX group, the PEMF group exhibited significantly increased BMD in the whole body, femur, and vertebral bodies. Micro-CT analysis results showed improved bone microstructure, significantly increased maximum load and bending strength of the femur, elevated levels of serum bone formation markers, and increased expression of osteogenic-related proteins. In conclusion, this study demonstrates that daily 90-minute exposure to 50 Hz-0.6 mT PEMF effectively enhances BMD, improves bone biomechanical properties, optimizes bone microstructure, stimulates bone formation, and inhibits bone resorption in ovariectomized rats, highlighting its therapeutic potential for postmenopausal osteoporosis.
Female ; Animals ; Rats, Sprague-Dawley ; Osteoporosis, Postmenopausal/therapy* ; Rats ; Bone Density ; Ovariectomy ; Magnetic Field Therapy/methods* ; Electromagnetic Fields

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

Background Non-suicidal self-injury(NSSI)behavior has become a major public health concern and can have significant implications for the physical and mental health of adolescents.Peer victimization is a risk factor for adolesents to have NSSI behavior,so exploring the relationship and underlying mechanism between peer victimization and NSSI functions will provide a promising strategy for the prevention and intervention of NSSI behavior.Objective To investigate the relationship between peer victimization and NSSI functions in adolescents with unipolar and bipolar depression,so as to provide references for the intervention of NSSI behavior in adolescent patients with unipolar and bipolar depression.Methods Using multi-stage stratified sampling,940 adolescents with unipolar and bipolar depression who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria for bipolar depressive episodes or depressive disorders were selected from 14 psychiatric hospitals in China.All participations were assessed using Chinese version of the Functional Assessment of Self-Mutilation(C-FASM),Multidimensional Peer-Victimization Scale(MPVS),UCLA Loneliness Scale(UCLA-LS)and Patient Health Questionnaire-9 item(PHQ-9).Pearson correlation coefficient was to assess the correlation among above scales,and the model fit and path coefficients for mediation were analyzed with model 4 in Process 4.0 for SPSS.Results A total of 698(74.26%)adolescents with unipolar and bipolar depression completed the questionnaire survey.NSSI behavior was detected in 374 patients(53.58%).Among adolescents with unipolar and bipolar depression and NSSI behavior,MPVS total score was positively correlated with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.104,0.130,0.266,P<0.05 or 0.01),UCLA-LS score also yielded a positive correlation with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.321,0.112,0.246,P<0.05 or 0.01),and UCLA-LS score was positively correlated with MPVS total score(r=0.241,P<0.01).Loneliness demonstrated a complete mediating role in the relationship between peer victimization and emotion regulation function,with an indirect effect value of 0.033(95%CI:0.019～0.050)and an effect size of 73.33%.A partial mediating effect of loneliness was also observed for the relationship between peer victimization and social avoidance function,with an indirect effect value of 0.016(95%CI:0.007～0.025)and an effect size of 17.98%.Conclusion Loneliness may act as a mediator in the relationship between the peer victimization and the NISS emotion regulation and social avoidance functions in adolescents with unipolar and bipolar depression and NSSI behaviors.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

Objective:To investigate the clinical outcomes and efficacy of trabecular metal (TM) cones for the reconstruction of metaphyseal bone defects in revision total knee arthroplasty.Methods:A retrospective analysis was conducted on 46 patients (47 knees), who underwent revision total knee arthroplasty with TM cones for metaphyseal defect reconstruction from July 2015 to August 2023. The cohort comprised 12 males and 34 females, ranging from 41 to 83 years of age, with a mean of 68.65 ± 9.09 years. Body mass index (BMI) ranged from 19.5 to 36.0 kg/m 2, averaging 27.20±4.50 kg/m 2. Bone defects were stratified according to the Anderson Orthopedic Research Institute (AORI) classification, including 64 sides (AORI T2B type 20 sides, T3 type 16 sides, F2B type 11 sides, F3 type 17 sides) which were addressed with 67 cones. Evaluations during follow-up included range of motion (ROM), visual analogue scale (VAS) for pain, and the American Knee Society Score (KSS). Long leg radiographs and knee X-rays were reassessed for femorotibial angle (FTA) and joint alignment, osseointegration of the TM cones, and any complications were documented. Results:The average follow-up duration was 46.22±26.55 months (range 16-103 months). The KSS knee score significantly improved from 29.22±19.79 preoperatively to 88.22±6.01 at the final follow-up ( F=258.118, P<0.001). Similarly, the KSS function score saw a marked increase from a preoperative average of 7.65±8.21 to 56.30±6.10 at the final follow-up ( F=354.711, P<0.001). VAS scores significantly decreased from 5.35±1.50 preoperatively to 0.28±0.50 at the final follow-up ( F=300.934, P<0.001). ROM improved from 67.72°±34.62° preoperatively to 85.33°±9.15° at the final follow-up ( F=7.798, P<0.001), and the FTA improved from 179.24°±10.30° preoperatively to 174.39°±1.69° at the final follow-up, a statistically significant enhancement ( F=9.123, P<0.001). Osseointegration was observed in 95.5% of the cases (64/67 cones). There were no instances of osteolysis or aseptic loosening observed, indicating stable prosthetic fixation. Complications were minimal, with one reported case of a femoral shaft fracture, which was successfully treated with internal fixation, resulting in satisfactory healing at 6 months. At the last follow-up (3 years after operation), the patient could walk at home with a walker and the other patients had no complications such as periprosthetic joint infection, dislocation and periprosthetic fracture. Conclusion:The application of trabecular metal cones in revision total knee arthroplasty provides an effective solution for the reconstruction of severe metaphyseal bone defects, enhancing prosthetic stability and restoring the knee joint's mechanical alignment. The trend towards successful osseointegration in the TM cones is promising, and a significant improvement in knee joint function has been observed.

Objective:To analyze the preoperative and postoperative serum cholinesterase (CHE) levels in patients with stage ⅠA-ⅢA breast cancer who underwent surgical treatment, and to explore the roles of them and peripheral blood inflammatory markers in the prognostic prediction of stage ⅠA-ⅢA breast cancer.Methods:The relevant blood indicators of 152 patients with stage ⅠA-ⅢA breast cancer who underwent surgery and postoperative adjuvant therapy from January 2012 to December 2017 at Affiliated Huai'an Hospital of Xuzhou Medical University were retrospectively studied. The optimal cut-off values of serum CHE levels and peripheral blood inflammatory markers [systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) ] were calculated using X-tile 3.6.1 software. Patients were categorized into low and high value groups based on the optimal cutoff values. Kaplan-Meier curves and Cox regression analysis were used to assess the correlation between CHE and peripheral blood inflammation indexes and disease-free survival (DFS). Spearman correlation coefficient and Wilcoxon test were used to assess the correlation and changes of CHE and inflammation indexes before and after treatment. In addition to this, a nomogram prediction model was conscturcted based on independent prognostic factors by R software, which was validated by Bootstrap method.Results:The CHE levels of patients before and after treatment was 8 645.0 (7 251.3, 10 229.3) and 9 309.0 (7 801.0, 10 835.3) U/L, respectively, with a statistically significant difference ( Z=2.73, P=0.006) .The optimal cut-off values for postoperative CHE (Post-CHE), postoperative SII (Post-SII), and postoperative SIRI (Post-SIRI) associated with patients' DFS, being 7 773 U/L, 741, and 0.9, respectively. Univariate analysis showed that tumor size (≤2 cm vs.>2 cm and ≤5 cm: HR=2.55, 95% CI: 1.30-4.99, P=0.006; ≤2 cm vs. >5 cm: HR=8.95, 95% CI: 4.15-19.32, P<0.001), number of positive lymph nodes ( HR=3.84, 95% CI: 2.24-6.58, P<0.001), clinical stage (stage Ⅰ vs. stage Ⅱ: HR=1.52, 95% CI: 0.68-3.39, P=0.309, stage Ⅰ vs. stage Ⅲ: HR=8.12, 95% CI: 3.76-17.55, P<0.001), Ki-67 expression ( HR=2.19, 95% CI: 1.24-3.84, P=0.007), whether radiotherapy ( HR=2.05, 95% CI: 1.19-3.53, P=0.010), Post-CHE ( HR=6.81, 95% CI: 3.94-11.76, P<0.001), Pre-neutrophil to lymphocyte ratio (NLR) ( HR=1.11, 95% CI: 1.02-1.21, P=0.014), Post-NLR ( HR=5.23, 95% CI: 2.78-9.85, P<0.001), Pre-platelet to lymphocyte ratio (PLR) ( HR=2.08, 95% CI: 1.01-4.26, P=0.046), Post-PLR ( HR=7.11, 95% CI: 3.78-13.37, P<0.001), Pre-lymphocyte to monocyte ratio (LMR) ( HR=0.37, 95% CI: 0.20-0.66, P<0.001), Post-LMR ( HR=0.23, 95% CI: 0.13-0.41, P<0.001), Pre-SII ( HR=1.81, 95% CI: 1.05-3.12, P=0.033), Post-SII ( HR=6.12, 95% CI: 3.48-10.76, P<0.001), Pre-SIRI ( HR=2.12, 95% CI: 1.24-3.63, P=0.006), and Post-SIRI ( HR=4.93, 95% CI: 2.87-8.48, P<0.001) were associated with DFS in patients with stage ⅠA-ⅢA breast cancer. Multivariate analysis showed that tumor size (≤2 cm vs. >2 cm and ≤5 cm: HR=2.86, 95% CI: 1.41-5.78, P=0.003; ≤2 cm vs. >5 cm: HR=3.72, 95% CI: 1.50-9.26, P=0.005), number of positive lymph nodes ( HR=4.66, 95% CI: 2.28-9.54, P<0.001), Ki-67 expression ( HR=2.13, 95% CI: 1.15-3.94, P=0.016), Post-CHE ( HR=0.18, 95% CI: 0.10-0.33, P<0.001), Post-SII ( HR=2.71, 95% CI: 1.39-5.29, P=0.004), and Post-SIRI ( HR=3.77, 95% CI: 1.93-7.36, P<0.001) were independent influencing factors for DFS in patients with stage ⅠA-ⅢA breast cancer. Kaplan-Meier survival curve analysis showed that the median DFS of patients in the Ki-67<30% group was not reached, and the median DFS of patients in the Ki-67≥30% group was 89.0 months, and the 3- and 5-year DFS rates were 84.9% vs. 75.9% and 80.8% vs. 64.3%, respectively, with a statistically significant difference ( χ2=7.65, P=0.006) ; the median DFS of patients in the tumor size≤2 cm group was not reached, the median DFS of the 2 cm5 cm group was 26.3 months, and the 3- and 5-year DFS rates were 95.5% vs. 74.6% vs. 42.1%, 86.3% vs. 68.6% vs. 25.3%, with a statistically significant difference ( χ2=40.46, P<0.001) ; the median DFS of patients in the group with the number of positive lymph nodes<4 was not reached, and the median DFS of the group with the number of positive lymph nodes≥4 was 30.7 months, and the 3- and 5-year DFS rates were 87.9% vs. 46.4% and 81.4% vs. 28.6%, respectively, with a statistically significant difference ( χ2= 47.34, P<0.001) ; the median DFS of patients in the Post-CHE<7 773 U/L group was 47.3 months, and the median DFS of patients in the Post-CHE≥7 773 U/L group was not reached, and the 3- and 5-year DFS rates were 52.8 % vs. 88.6% and 27.8% vs. 81.2%, respectively, with a statistically significant difference ( χ2=62.17, P<0.001) ; the median DFS was not achieved in patients in the Post-SII<741 group, and the median DFS was 30.5 months in the Post-SII≥741 group, with 3- and 5-year DFS rates of 88.1% vs. 38.5% and 80.1% vs. 30.8%, respectively, with a statistically significant difference ( χ2=50.78, P<0.001) ; the median DFS of patients in Post-SIRI<0.9 group was not reached, the median DFS of Post-SIRI≥0.9 group was 33.3 months, and the 3- and 5-year DFS rates were 93.5% vs. 46.7% and 84.9% vs. 39.9%, respectively, with a statistically significant difference ( χ2=40.67, P<0.001). Spearman correlation analysis revealed that Post-CHE was not correlated with Post-SII ( r=-0.111, P=0.175), and Post-CHE was negatively correlated with Post-SIRI ( r=-0.228, P=0.005). Post-treatment CHE was elevated compared to preoperative and the median DFS was not reached in patients with elevated CHE group and 61.8 months in patients with reduced CHE group after treatment, with a statistically significant difference ( χ2=25.67, P<0.001). The nomogram based on independent prognostic factors had good predictive performance, with a C-index of 0.893. Conclusion:The serum CHE level exhibited a significant increase following treatment. Postoperative serum CHE combined with SII and SIRI can effectively predict DFS in patients with stage ⅠA-ⅢA breast cancer, and the prognosis of patients with elevated CHE after treatment is better. The nomogram constructed based on independent prognostic factors has good predictive performance for DFS in breast cancer patients.