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.

Objective To detect the expression of N-acetyltransferase 10(NAT10)and polyadenylate bind-ing protein cytoplasmic 1(PABPC1)in non muscle invasive bladder cancer(NMIBC),and analyze the correla-tion between them and epithelial mesenchymal transition(EMT)and prognosis.Methods A total of 122 pa-tients with NMIBC treated in the hospital from May 2019 to May 2021 were selected.Immunohistochemistry was used to detect the expression of NAT10 and PABPC1 proteins in NMIBC tissues.Real time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the expression of NAT10,PABPC1 mRNA,and EMT markers in NMIBC tissues.Pearson correlation analysis was conducted on the correlation between EMT indicators[Snail,N-cadherin(N-cad),vimentin(Vim)mRNA].Cox regression analysis was conducted on the relationship between NAT10,PABPC1 and prognosis of NMIBC.Results Compared with adjacent tis-sues,the expression of NAT10 mRNA,PABPC1 mRNA,Snail mRNA,N-cad mRNA,and Vim mRNA in NMIBC cancer tissues was higher,and the difference was statistically significant(P＜0.001).The expression of NAT10 mRNA,PABPC1 mRNA in NMIBC cancer tissues was positively correlated with Snail mRNA,N-cad mRNA,and Vim mRNA(r=0.678,0.702,0.711,0.754,0.788,0.663,P＜0.001).The positive rates of NAT10 and PABPC1 in NMIBC cancer tissues were 59.02％(72/122)and 60.66％(74/122),respectively,while those in adjacent tissues were 6.56％(8/122)and 4.92％(6/122),respectively(x2=76.176,85.995,P＜0.001).The positive rates of NAT10 and PABPC1 in NMIBC cancer tissues were higher than those in ad-jacent tissues,and the difference was statistically significant(x2=76.176,85.995,P＜0.001).The positivity rates of NAT10 and PABPC1 in cancer tissues of stage T1,high-grade NMIBC patients were higher than those in cancer tissues of Ta/Ti,low-grade patients,and the differences were statistically significant(P＜0.05).The 3-year overall progression free survival rates of NMIBC patients in the NAT10 positive and negative groups were 48.61％(35/72)and 80.00％(40/50),respectively,with a statistically significant difference(Log rank x2=13.780,P=0.000).The 3-year overall progression free survival rates of PABPC1 positive and negative patients were 47.30％(35/74)and 83.33％(40/48),respectively,with a statistically significant difference(Log rank x2=11.830,P=0.001).T1 stage,high-grade,NAT10 positive,and PABPC1 positive were risk fac-tors affecting the prognosis of NMIBC.Conclusion The expression of NAT10 and PABPC1 in NMIBC cancer tissue is significantly upregulated and positively correlated with EMT markers,which is correlated with poor prognosis of NMIBC.

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

Objective:To evaluate the relationships between the location and extent of diffusion of free intraperitoneal air by multi-slice spiral CT (MSCT) and between the location and size of acute gastrointestinal perforation.Methods:This was a descriptive case series. We examined abdominal CT images of 33 patients who were treated for intraoperatively confirmed gastrointestinal perforation (excluding appendiceal perforation) in the Department of General Surgery, Nanfang Hospital between January and September 2022. We identified five locations of intraperitoneal air: the subphrenic space, hepatic portal space, mid-abdominal wall, mesenteric space, and pelvic cavity. We allocated the 33 patients to an upper gastrointestinal perforation ( n=23) and lower gastrointestinal perforation group ( n=10) base on intraoperative findings and analyzed the relationships between the locations of free gas and of gastrointestinal perforation. Additionally, we established two models for analyzing the extent of diffusion of free gas in the abdominal cavity and constructed receiver operating characteristic (ROC) curves to analyze the relationships between the two models and the size of the gastrointestinal perforation. Results:In the upper gastrointestinal perforation group, free gas was located around the hepatic portal area in 91.3% (21/23) of patients: this is a significantly greater proportion than that found in the lower gastrointestinal perforation group (5/10) ( P=0.016). In contrast, free gas was located in the mesenteric interspace in 8/10 patients in the lower gastrointestinal perforation group; this is a significantly greater proportion than was found in the upper gastrointestinal perforation group (8.7%, 2/23) ( P<0.010). The sensitivity of diagnosis of upper gastrointestinal perforation base on the presence of hepatic portal free gas was 84.8% and the specificity 71.4%. Further, the sensitivity of diagnosis of lower gastrointestinal perforation base on the presence of mesenteric interspace free gas was 80.0% and the specificity 91.3%. The rates of presence of free gas in the subdiaphragmatic area, mid-abdominal wall, and pelvic cavity did not differ significantly between the two groups (all P>0.05). Receiver operating characteristic curves showed that when free gas was present in four or more of the studied locations in the abdominal cavity, the optimal cutoff for perforation diameter was 2 cm, the corresponding sensitivity 66.7%, and the specificity 100%, suggesting that abdominal free gas diffuses extensively when the diameter of the perforation is >2 cm. Another model revealed that when free gas is present in three or more of the studied locations, the optimal cutoff for perforation diameter is 1 cm, corresponding to a sensitivity of 91.7% and specificity of 76.2%; suggesting that free gas is relatively confined in the abdominal cavity when the diameter of the perforation is <1 cm. Conclusion:Identifying which of five locations in the abdominal cavity contains free intraperitoneal air by examining MSCT images can be used to assist in the diagnosis of the location and size of acute gastrointestinal perforations.

Objective To investigate the effect and mechanism of a high uric acid environment on cataract formation by rat lens ex-vivo culture model.Methods The lenses harvested from adult Sprague Dawley rats were cultured in a high uric acid environment in vitro.The lenses were divided into the blank control group(15 eyes)and the uric acid treatment group(15 eyes).The lenses in the uric acid treatment group were treated with M-199 medium with 800 μmol·L-1 uric acid and lenses in the blank control group were cultured with M-199 medium without uric acid for 7 days.The turbidity of the lenses of rats in the two groups was observed by optical microscope.The deposition of urate in the lenses of rats in the two groups was detected by the Gomori hexamine silver method.The senescence of lens cells in the two groups was measured by SA-[3-gal staining.Lens cell apoptosis in the two groups was detected by the TUNEL method.Results The opacifica-tion in lenses of the uric acid treatment group occurred on the 5th day and the opacification grade significantly increased on the 7th day,with opacification grades being significantly different from those in the blank control group(both P＜0.05).In the blank control group,the lens epithelial cells were arranged neatly with no urate deposition,a few blue-stained lens epi-thelial cells and no obvious positive cells.In the uric acid treatment group,the arrangement of the lens epithelial was disor-dered in the equatorial part of the lens and under the anterior capsule,with black-brown urate crystals around the lens,more blue-stained lens epithelial cells and a small number of positive cells.In the high uric acid environment,urate crystals deposited under the capsular membrane of the lens,the surrounding lens epithelial cells were senescent,and a small num-ber of lens epithelial cells died.Conclusion A high uric acid environment can steadily and effectively induce cataract formation in the rat lens ex-vivo culture model.The mechanism may be related to senescence and apoptosis of lens epitheli-al cells induced by uric acid.

Objective A simulation study was conducted to explore the effect and performance of g-computation-based joint mixed-effects model(JMM)on causal inference for controlling unmeasured confounders in longitudinal studies.Methods Longitudinal data including baseline and two follow-up visits were generated by computer simulations.The simulation scenarios included different sample sizes,the presence or absence of unmeasured confounders,and effects of unmeasured confounders.Causal effects were estimated using g-computation-based JMM,linear mixed-effects model,fixed effects model,and longitudinal target maximum likelihood estimation,respectively.Indicators including mean absolute deviation(MAD),standard error,root mean square error(RMSE),and 95%confidence interval coverage(95%CI coverage)were used to evaluate and compare the causal inference performance.Based on the physical examination cohort data of the menopausal women,four models were used to estimate the causal association between serum follicle-stimulating hormone(FSH)levels and lumbar bone density in menopausal women respectively,verifying the causal inference performance of models in the real longitudinal data.Results JMM had a better accuracy of causal inference with controlling unmeasured confounders.But its estimation stability was slightly worse.When strong unmeasured confounders existed,only JMM can accurately estimate the causal effect,and its precision and authenticity were better in scenarios with large sample sizes.Conclusion JMM can effectively control the unmeasured confounders and perform approximately unbiased causal estimation in longitudinal studies.

Objective:To explore the in vitro antibacterial effects of low-intensity pulsed ultrasound (LIPUS) combined with 3.5 g/L povidone iodine solution on the biofilm of methicillin-resistant staphylococcus aureus (MRSA). Methods:Immature (cultured for 24 hours) and mature (cultured for 72 hours) MRSA biofilms were established on the surfaces of glass slides or confocal dishes. They were randomly divided into 4 groups ( n=9) according to different intervention methods. In the control group, glass slides or confocal dishes were placed in 500 mL of physiological saline for 3 minutes; in the PI group, glass slides or confocal dishes were placed in 500 mL of 3.5 g/L povidone iodine solution for 3 minutes; in the LIPUS group, glass slides or confocal dishes were placed in 500 mL of physiological saline and simultaneously intervened with LIPUS for 3 minutes; in the LIPUS & PI group, glass slides or confocal dishes were placed into 500 mL of 3.5 g/L povidone iodine solution and simultaneously intervened with LIPUS for 3 minutes. After intervention, confocal microscopy (CLSM) and scanning electron microscopy (SEM) were used to observe and compare the structure, morphology, bacterial survival, and viable cell count of the MRSA biofilms among the 4 groups. Results:On the MRSA biofilms cultured for 24 and 72 hours, CLSM and SEM observed sparse biofilms in the LIPUS group and LIPUS & PI group, and also a large number of dead bacteria in the LIPUS & PI group. On the MRSA biofilms cultured for 24 hours, the bacterial colony counts in the control group, PI group, LIPUS group, and LIPUS & PI group were (1.21±0.45)×10 6 CFU/mL, (3.38±2.81)×10 3 CFU/mL, (1.82±0.37)×10 3 CFU/mL, and (69.67±27.93) CFU/mL, respectively. Except for the comparison between PI group and LIPUS group, which showed no statistically significant difference ( P>0.05), there were statistically significant differences between the other groups when compared pairwise ( P<0.05). On the MRSA biofilms cultured for 72 hours, the bacterial colony counts in the control group, PI group, LIPUS group, and LIPUS & PI group were (3.01±0.70)×10 6 CFU/mL, (1.80±1.52)×10 5 CFU/mL, (2.10±0.52)×10 3 CFU/mL, and (68.67±19.55) CFU/mL, respectively. There were statistically significant differences between the 4 groups when compared pairwise ( P<0.05). Conclusions:Application of LIPUS or 3.5 g/L povidone iodine alone for 3 minutes on the immature or mature MRSA biofilms in vitro only leads to partial antibacterial activity. However, LIPUS can enhance the in vitro antibacterial effect of 3.5 g/L povidone iodine on the MRSA biofilms at different maturity levels.

Objective:To evaluate the clinical efficacy of single-stage total hip arthroplasty (THA) combined with intra-articular antibiotic injection in managing postoperative infections following internal fixation of hip fractures.Methods:A retrospective analysis was conducted on 25 patients who underwent single-stage THA for infection following internal fixation of hip fractures from January 2013 to January 2021 at the Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University. The cohort comprised 15 males and 10 females, with an average age of 61.52±13.06 years (range, 32-89 years) and an average body mass index of 24.04±3.84 kg/m 2 (range, 18-34 kg/m 2). The fractures included 13 femoral neck fractures, 6 intertrochanteric fractures, 4 acetabular fractures, 1 proximal femoral fracture, and 1 combined acetabular and intertrochanteric fracture. Preoperative joint cavity puncture or intraoperative joint fluid extraction, biochemical analysis, microbial culture, and drug sensitivity tests were performed. During surgery, infected internal fixation devices were removed, and hip prostheses were implanted following thorough debridement. Postoperatively, patients received intravenous and intra-articular sensitive antibiotics based on bacterial culture and drug sensitivity results. Joint stability was evaluated according to the Engh standard, and hip function was assessed using the Harris score. Results:Microbial cultures were positive in 12 cases, identifying Staphylococcus epidermidis (4 cases), Staphylococcus aureus (2 cases), Escherichia coli (2 cases), Enterobacter cloacae (1 case), Pseudomonas aeruginosa (1 case), Corynebacterium striatum (1 case), and a mixed infection of Staphylococcus epidermidis and Enterococcus faecalis (1 case). All 25 patients were followed for an average of 56.64±26.38 months (range, 24-123 months). Intravenous and intra-articular antibiotic treatment was administered to all patients. One case experienced sinus tract formation and pus discharge on the 20th postoperative day, diagnosed as periprosthetic infection, resulting in treatment failure, yielding an infection control rate of 96% (24/25). All patients demonstrated stable prosthesis fixation with no subsidence, loosening, or osteolysis. At the final follow-up, the Harris hip score improved significantly from a preoperative score of 26.69±13.47 to 92.30±5.60 ( t=22.882, P<0.001). Complications included 2 cases of hip dislocation, 2 cases of deep venous thrombosis in the lower extremities, 1 case of poor wound healing, and 1 case of periprosthetic fracture. Conclusion:Single-stage THA combined with intra-articular antibiotic injection is effective in controlling infections following internal fixation of hip fractures. This approach not only achieves a high infection control rate but also reconstructs hip joint function, resulting in satisfactory postoperative outcomes.