Objective:To investigate the risk factors for new adjacent vertebral fracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fracture (OVCF) and their predictive efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 476 OVCF patients admitted to The Affiliated Wuxi People′s Hospital of Nanjing Medical University from January 2018 to December 2024, including 74 males and 402 females, aged 49-91 years [71(65, 79)years]. Among them, 397 patients underwent single-level PKP, while 79 received multi-level PKP. Surgical segments involved T 6 in 9 patients, T 7 in 9, T 8 in 14, T 9 in 12, T 10 in 9, T 11 in 50, T 12 in 110, L 1 in 173, L 2 in 77, L 3 in 46, L 4 in 31, and L 5 in 13. The patients were divided into adjacent vertebral fracture group ( n=55) and non-adjacent vertebral fracture group ( n=421) according to whether adjacent vertebral fracture was observed during the follow-up. The following data were collected in both groups: gender, age, body mass index (BMI), bone mineral density T-value, underlying diseases (hypertension, diabetes, coronary heart disease), prior cerebral infarction, history of OVCF, long-term glucocorticoid use, thoracolumbar fracture, number of operated vertebrae, cement injection approach (unilateral or bilateral), mean cement dose, postoperative vertebral height restoration rate, postoperative Cobb angle correction, postoperative thoracolumbar kyphosis angle correction, and cement distribution score. Univariate and multivariate Logistic stepwise regression analysis were performed to assess and identify independent risk factors for adjacent vertebral fracture in OVCF patients after PKP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the risk factors′ predictive performance for adjacent vertebral fracture in OVCF patients after PKP. Results:Univariate analysis revealed significant differences in age, bone mineral density T-value, history of OVCF, long-term glucocorticoid use, number of operated vertebrae, and cement distribution score between the two groups ( P<0.05). The multivariate Logistic stepwise regression analysis showed that the bone mineral density T-value ( OR=0.68, 95% CI 0.48, 0.95, P<0.05) and cement distribution score ( OR=0.61, 95% CI 0.49, 0.76, P<0.01) were significantly correlated with new adjacent vertebral fractures after PKP. The ROC curve analysis showed that bone cement distribution score showed better predictive performance (AUC=0.72, 95% CI 0.64, 0.79), compared with bone mineral density T-value (AUC=0.62, 95% CI 0.54, 0.70), while the combined predictive performance of the two factors was the best (AUC=0.75, 95% CI 0.68, 0.81). Conclusions:Bone mineral density T-value and cement distribution score are independent risk factors for new adjacent vertebral fracture in OVCF patients after PKP. The predictive performance of cement distribution score is proved to be good and can be better in combination with bone mineral density T-value.

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5％imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.

Objective:To investigate the risk factors for new adjacent vertebral fracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fracture (OVCF) and their predictive efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 476 OVCF patients admitted to The Affiliated Wuxi People′s Hospital of Nanjing Medical University from January 2018 to December 2024, including 74 males and 402 females, aged 49-91 years [71(65, 79)years]. Among them, 397 patients underwent single-level PKP, while 79 received multi-level PKP. Surgical segments involved T 6 in 9 patients, T 7 in 9, T 8 in 14, T 9 in 12, T 10 in 9, T 11 in 50, T 12 in 110, L 1 in 173, L 2 in 77, L 3 in 46, L 4 in 31, and L 5 in 13. The patients were divided into adjacent vertebral fracture group ( n=55) and non-adjacent vertebral fracture group ( n=421) according to whether adjacent vertebral fracture was observed during the follow-up. The following data were collected in both groups: gender, age, body mass index (BMI), bone mineral density T-value, underlying diseases (hypertension, diabetes, coronary heart disease), prior cerebral infarction, history of OVCF, long-term glucocorticoid use, thoracolumbar fracture, number of operated vertebrae, cement injection approach (unilateral or bilateral), mean cement dose, postoperative vertebral height restoration rate, postoperative Cobb angle correction, postoperative thoracolumbar kyphosis angle correction, and cement distribution score. Univariate and multivariate Logistic stepwise regression analysis were performed to assess and identify independent risk factors for adjacent vertebral fracture in OVCF patients after PKP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the risk factors′ predictive performance for adjacent vertebral fracture in OVCF patients after PKP. Results:Univariate analysis revealed significant differences in age, bone mineral density T-value, history of OVCF, long-term glucocorticoid use, number of operated vertebrae, and cement distribution score between the two groups ( P<0.05). The multivariate Logistic stepwise regression analysis showed that the bone mineral density T-value ( OR=0.68, 95% CI 0.48, 0.95, P<0.05) and cement distribution score ( OR=0.61, 95% CI 0.49, 0.76, P<0.01) were significantly correlated with new adjacent vertebral fractures after PKP. The ROC curve analysis showed that bone cement distribution score showed better predictive performance (AUC=0.72, 95% CI 0.64, 0.79), compared with bone mineral density T-value (AUC=0.62, 95% CI 0.54, 0.70), while the combined predictive performance of the two factors was the best (AUC=0.75, 95% CI 0.68, 0.81). Conclusions:Bone mineral density T-value and cement distribution score are independent risk factors for new adjacent vertebral fracture in OVCF patients after PKP. The predictive performance of cement distribution score is proved to be good and can be better in combination with bone mineral density T-value.

Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5％imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

BACKGROUND:Calcium phosphate(CaP)coatings are widely used to improve the integration of titanium implants into bone but these coatings are associated with risks of infection.It is thus desirable to confer antibacterial properties to CaP coatings. OBJECTIVE:To prepare CaP-MgO composite coatings by impregnating magnesium oxide(MgO)sol into CaP coatings and assess the in vitro antibacterial activities and cytocompatibility. METHODS:An electrolyte was determined by titration and used for CaP coating electrodeposition on titanium(referred to as Ti-CaP).MgO was impregnated into the coating by immersing in an MgO sol with different mass fractions(15%,30%,50%)and subsequently calcined to form MgO-CaP composite coatings,which were recorded as Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg,respectively.Microstructure,tensile properties,critical load,and Mg2+ release of coatings in vitro were characterized.Antibacterial activity was assayed using spread plate method by culturing S.aureus on the pure titanium sheet surface and Ti-CaP,Ti-Cap-15mg,Ti-Cap-30mg and Ti-Cap-50mg surfaces for 24 and 48 hours.Mouse osteoblast suspension was inoculated on pure titanium sheets and Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg coated titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay,and cell survival rate was calculated.The morphology of composite coating soaked in DMEM was also observed. RESULTS AND CONCLUSION:(1)Homogeneous,microporous CaP coatings consisting of octacaclium phosphate crystal flakes were prepared on titanium by electrodeposition.After sol impregnation-calcination,MgO aggregates were filled into the inter-flake voids.The extent of MgO filling and Mg concentration in the coating increased with the number of sol impregnation procedures.When immersed in phosphate buffered saline,all composite coatings actively released Mg2+ within 1 day;subsequently,the Mg2+ release slowed down on day 3.A small amount of Mg2+ release was still detected on day 7.The yield strength,tensile strength and fracture growth rate of Ti-CaP-30Mg coated titanium were not significantly different from those of pure titanium(P>0.05).There was no significant difference in the critical load of Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups(P>0.05).(2)Except that pure titanium sheet and Ti-CaP had no antibacterial properties,the other samples had good antibacterial properties,and the antibacterial rate increased with the increase of MgO content in the coating.(3)After 1 and 3 days of co-culture,the cell survival rate of Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups was lower than that of pure titanium group and Ti-CaP group(P<0.05).After 5 and 7 days of culture,there was no significant difference in cell survival rate among five groups(P>0.05).The content of MgO in the coating decreased gradually with the time of immersion in the medium.(4)The MgO sol impregnation added antibacterial properties to the CaP coatings while retained their biocompatibility.

Objective:To evaluate the efficacy and safety of high-dose injectable dexlansoprazole in the treatment of acute upper gastrointestinal ulcer hemorrhage.Methods:This study was a randomized, double-blind, positive drug parallel controlled, multicenter clinical trial led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), with participation from 43 hospitals such as Yichun People′s Hospital, Army Medical Center of PLA (Chongqing Daping Hospital), etc. From August 31, 2019 to May 25, 2020, 346 patients with upper gastrointestinal hemorrhage caused by acute gastric and (or) duodenal ulcer were selected. The subjects were randomly divided into experimental group and control group according to a 2 to 1 stratification scheme using the SAS 9.4 software. The medication regimen for the experimental group was intravenous injection of dexlansoprazole 30 mg/times, once every 12 h, while the medication regimen for the control group was intravenous injection of lansoprazole and dexlansoprazole mimetics, 30 mg/times, once every 12 h; the treatment course was 5 days. The primary efficacy indicator (72 h effective hemostasis rate), the secondary efficacy indicator(clinical hemostasis rate at 24, 48, and 120 h, and the proportion of subjects who underwent endoscopic treatment or surgical procedures again due to hemorrhage within 5 days), and the incidence of adverse reactions were compared between the 2 groups. Binomial distribution normal approximation method was performed to calculate the 95% confidence interval (95% CI) of the difference in hemostasis rate between the experimental group and the control group. Fisher′s exact test was used for statistical analysis. Results:A total of 329 patients (219 cases in the experimental group and 110 cases in the control group) were enrolled. The 72 h effective hemostasis rate (95% CI) of the experimental and control group was 95.9%(210/219, 92.3% to 98.1%) and 93.6%(103/110, 87.3% to 97.4%), respectively, and the difference was not statistically significant ( P>0.05). The difference in the 72-hour effective hemostasis rate(95% CI) between the experimental and the control group was 2.3% (-3.0% to 7.5%). The clinical hemostasis rates at 24, 48, and 120 h of the treatment were 82.2% (176/214), 99.1%(210/212), and 100.0%(210/210) in the experimental group, and 85.2%(92/108), 98.1%(104/106), and 100.0%(105/105) in the control group, respectively, and the differences were not statistically significant (all P>0.05). The proportion of subjects who underwent endoscopic treatment and surgical procedure again within 5 days (95% CI)of the experimental group and control group was 0 (0 to 1.7%) and 1.9% (0.2% to 6.5%), respectively, and the difference was not statistically significant ( P>0.05). The result of safety evaluation showed that the overall incidence of adverse reactions of the experimental group and the control group was 6.4% (14/219) and 11.8% (13/110), respectively, and the difference was not statistically significant ( P>0.05). Conclusion:High dose injectable dexlansoloprazole is an effective and safe treatment for upper gastrointestinal ulcer hemorrhage, and suitable for clinical application.