BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective:To assess the burden and development trends of tuberculosis (TB) in China from 1990 to 2021 to provide a reference for TB prevention strategies.Methods:Utilizing the 2021 Global Burden of Disease Study data, the study evaluates the burden of TB and latent TB infection (LTBI) in China using age-standardized incidence, prevalence, disability-adjusted life years (DALYs), and infection rates. The Joinpoint regression model was employed to analyze changing trends, and the autoregressive moving average model was integrated to forecast multidrug-resistant TB incidence and LTBI infection rates from 2022 to 2030.Results:In 2021, the age-standardized TB incidence in China was 36.28 per 100 000, the age-standardized prevalence was 30 557.45 per 100 000, the age-standardized DALY rate was 76.22 per 100 000, and the LTBI age-standardized infection rate was 30.48%. Compared to 1990, these figures dropped by 66.72%, 2.82%, 89.41%, and 2.47%, respectively. The age-standardized incidence, prevalence, DALY rate, and infection rate were elevated in individuals aged ≥70 years, and the TB burden was greater in males than in females. The age-standardized TB incidence declined between 1990 and 2021, while the proportion of multidrug-resistant TB patients among newly diagnosed cases, nationwide rose from 3.11% (36 367/1 167 807) in 1990 to 4.12% (25 431/617 725) in 2021. The LTBI age-standardized infection rate exhibited a fluctuating declining trend, averaging a decrease of 0.09%. Predictions for 2022-2030 indicate that China's multidrug-resistant TB incidence will decline slowly, and the LTBI infection rate will initially rise and then gradually fall, reaching 1.10/100 000 and 31.11%, respectively, by 2030.Conclusions:The TB burden in China declined from 1990 to 2021, but TB prevalence and LTBI infection rates remain high, especially among multidrug-resistant cases, males, and the elderly. Implementing systematic LTBI interventions, enhancing early detection/diagnosis in key populations such as the elderly, and promoting short-course treatments are recommended.

Objective:To assess the burden and development trends of tuberculosis (TB) in China from 1990 to 2021 to provide a reference for TB prevention strategies.Methods:Utilizing the 2021 Global Burden of Disease Study data, the study evaluates the burden of TB and latent TB infection (LTBI) in China using age-standardized incidence, prevalence, disability-adjusted life years (DALYs), and infection rates. The Joinpoint regression model was employed to analyze changing trends, and the autoregressive moving average model was integrated to forecast multidrug-resistant TB incidence and LTBI infection rates from 2022 to 2030.Results:In 2021, the age-standardized TB incidence in China was 36.28 per 100 000, the age-standardized prevalence was 30 557.45 per 100 000, the age-standardized DALY rate was 76.22 per 100 000, and the LTBI age-standardized infection rate was 30.48%. Compared to 1990, these figures dropped by 66.72%, 2.82%, 89.41%, and 2.47%, respectively. The age-standardized incidence, prevalence, DALY rate, and infection rate were elevated in individuals aged ≥70 years, and the TB burden was greater in males than in females. The age-standardized TB incidence declined between 1990 and 2021, while the proportion of multidrug-resistant TB patients among newly diagnosed cases, nationwide rose from 3.11% (36 367/1 167 807) in 1990 to 4.12% (25 431/617 725) in 2021. The LTBI age-standardized infection rate exhibited a fluctuating declining trend, averaging a decrease of 0.09%. Predictions for 2022-2030 indicate that China's multidrug-resistant TB incidence will decline slowly, and the LTBI infection rate will initially rise and then gradually fall, reaching 1.10/100 000 and 31.11%, respectively, by 2030.Conclusions:The TB burden in China declined from 1990 to 2021, but TB prevalence and LTBI infection rates remain high, especially among multidrug-resistant cases, males, and the elderly. Implementing systematic LTBI interventions, enhancing early detection/diagnosis in key populations such as the elderly, and promoting short-course treatments are recommended.

Objective:Pediatric chronic sinusitis （CRS） is a common disease within the field of otolaryngology-head and neck surgery. Due to the immaturity of sinus development and immune competence in children, its etiology and pathophysiology are complex, and its clinical features and outcomes differ significantly from those in adult patients. Currently, there are issues in the diagnosis and treatment of pediatric CRS, particularly in areas such as antibiotic use and surgical interventions, owing to a lack of sufficient attention. In recognition of this, the Chinese Rhinopathy Research Cooperation Group developed this expert consensus based on a systematic review of the latest literatures from both domestic and international sources, with reference to the latest evidence-based medical evidence worldwide, and in combination with their own clinical experience. The consensus covers various aspects including epidemiology, predisposing factors, pathophysiology, diagnosis and differential diagnosis, as well as treatment strategies such as medical therapy and surgical intervention. It aims to standardize the clinical diagnosis and treatment of pediatric CRS, improve clinical efficacy and patient satisfaction, reduce clinical expenditures, and decrease the occurrence of adverse reactions.
Humans ; Sinusitis/therapy* ; Chronic Disease ; Child ; Consensus ; Anti-Bacterial Agents/therapeutic use*

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth

The malignant degree of cholangiocarcinoma is high, and the early diagnosis is difficult. The vast majority of patients are unresectable when they are diagnosed. The patients have low quality of life and short survival cycle. Traditional radiotherapy and chemotherapy have poor efficacy and lead to side effects, and thus lack effective control measures for cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography (ERCP) is an important method for diagnosing and treating biliary tract diseases. Photodynamic therapy (PDT) is a new local treatment for cholangiocarcinoma. In recent years, ERCP-mediated PDT treatment of cholangiocarcinoma has gradually emerged. ERCP-mediated PDT can effectively relieve the symptoms of patients with cholangiocarcinoma, improve the patients' quality of life, prolong the survival cycle, and is expected to become a new treatment for cholangiocarcinoma.
Bile Duct Neoplasms ; diagnosis ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; diagnosis ; Cholangiopancreatography, Endoscopic Retrograde ; Humans ; Photochemotherapy ; Quality of Life

Objective:To test the validity and reliability of the Perceived Stress Scale-14 items (PSS-14) applied in cancer survivors.Methods:Totally 652 cancer survivors (patients who had finished active treatments and were in convalescence) were selected and a field questionnaire survey was conducted among them.Exploratory factor analysis and confirmatory factor analysis were performed to test the construct validity of PSS-14.Correlation between the two dimensions (discriminant validity) and correlation between stress and quality of life were analyzed to further test its validity.The intemal consistency reliability,split-half reliability,retest reliability and sensitivity analysis were adopted to test the reliability of PSS-14.Results:Two common factors were extracted in the exploratory factor analysis.The cumulative percentage of variance explained was 60.8％.The index of confirmatory factor analysis were:TLI =0.92,CFI =0.93,SRMR =0.07,RMSEA =0.08.The correlation coefficient between the two dimensions of PSS-14 was-0.16 (P ＜0.001).The correlation coefficients between the score of PSS-14 and each dimension of EORTC QLQ-C30 were 0.24-0.55 (P ＜ 0.001).The Cronbach α coefficients of the whole scale and the two dimensions named "perceived coping ability" and "perceived distress" were 0.78,0.91 and 0.88 respectively.After the scale was split into two parts,the Cronbach α coefficients of each part were 0.66 and 0.60.The Spearman-Brown coefficient was 0.79.The Guttman split-half coefficient was 0.79.After one item was removed from the scale each time,the Cronbach a coefficients of the remaining items varied from 0.75 to 0.77.The retest reliability of the whole scale and the two dimensions were 0.89,0.86 and 0.85 respectively.Conclusion:PSS-14 shows favorable validity and reliability,suggesting the utility to assess stress of cancer survivors as a self-administered inventory.