BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective To investigate the effect of KH-type splicing regulatory protein(KHSRP)on the malignant biological behavior of lung adenocarcinoma(LUAD)by targeting the Janus kinase 1(JAK1)/signal transducer and activator of transcription 3(STAT3)signaling axis.Methods Clinical data were collected for 64 patients with LUAD,diagnosed at Huaihe Hospital from January 2017 to December 2018.Expression levels of KHSRP were detected in LUAD tissues and adjacent tissues by immunohistochemical staining.KHSRP gene expression was also detected in LUAD cell lines(SPC-A1,H1975,CL1-5,PC-9,Calu-3,H446)and normal human bronchial epithelial cells using quantitative reverse transcription-polymerase chain reaction.KHSRP expression in SPC-A1,H1975,PC-9,and Calu-3 cells was manipulated by lentivirus transfection.The effects of KHSRP on the proliferation,migration,and invasion of LUAD cells were detected by Cell Counting Kit-8 and Transwell assays.The effects of KHSRP overexpression and knockdown were also investigated in a mouse xenograft tumor model,and JAK/STAT signaling pathway proteins were detected by Western blot.Rescue experiments were conducted to verify if KHSRP promoted the malignant progression of LUAD cells by regulating the JAK1/STAT3 signaling pathway.Results KHSRP expression was significantly higher in LUAD tissues compared with adjacent tissues(P＜0.05).Overexpression of KHSRP significantly promoted the proliferation,migration,and invasion of LUAD cells in vitro(P＜0.05).KHSRP also promoted LUAD cell xenograft tumor growth and lung nodule metastasis in nude mice in vivo(P＜0.01).KHSRP knockdown significantly decreased the levels of JAK1,phospho-JAK1,and STAT3 in the JAK/STAT signaling pathway,while the situation was reversed following KHSRP overexpression(P＜0.05).Rescue experiments showed that KHSRP reversed the inhibitory effect of knockdown(P＜0.05).Conclusions KHSRP targets the JAK1/STAT3 signaling pathway and acts as an oncogene in LUAD.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective To investigate the clinical value of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy.Methods The clinical data of 6 patients with esophageal stricture lesions with EUS-FNA that cannot be clearly diagnosed by endoscopic general biopsy from January 2021 to Jun 2023 were retrospectively analyzed,and the accuracy of EUS-FNA was analyzed for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy,while the results of surgery pathology or final follow-up results was taken as the diagnostic criteria.Results All the patients underwent EUS-FNA.The puncture clearly diagnosed 5 cases of malignancy and 1 case of chronic inflammation.Among them,5 patients underwent surgical operations,and the postoperative pathological findings were consistent with the puncture pathology.One patient was followed up for a long time and had repeated gastroscopy.There was no evidence of malignant tumor in the clinical manifestations and routine gastroscopic findings,so it was still considered to be an inflammatory change,which was consistent with the puncture pathological result.All patients had no complications,including abdominal pain,bleeding,perforation,and infection.Conclusion EUS-FNA is an effective and safe method for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy and has high clinical application value.

Objective To quantify the association between obesity and erectile dysfunction (ED) risk through a meta-analysis. Methods Following PRISMA guidelines, systematic searches of Chinese and English databases (up to March 2025) were conducted to include observational studies (cohort, cross-sectional, case-control). Adjusted effect sizes (OR and 95% CI) were extracted. Study quality was assessed using the Agency for Healthcare Research and Quality(AHRQ) scale, and a random-effects model was applied to pool effect sizes. Subgroup analyses (geographic region, obesity definitions) and sensitivity analyses were performed to validate robustness. Results Ten studies (n=230 744), including nine cross-sectional studies, were included. The meta-analysis revealed that obesity significantly increased ED risk (random-effects OR=1.80, 95% CI: 1.29-2.51), with high heterogeneity (I2=99.9%). Subgroup analyses indicated stronger associations in USA populations (OR=2.10, 95% CI: 1.23-3.60) than in Chinese populations (OR=1.16, 95% CI: 1.05-1.28). The highest effect size was observed when using BMI≥25 kg/m3 as the obesity threshold (OR=3.05, 95% CI: 2.06-4.51). Sensitivity analyses confirmed robust results (OR: 1.60-1.94 after excluding any single study). Conclusions Obesity is a critical risk factor for ED, with effect strength influenced by geographic region and obesity definitions. Interventions targeting BMI≥30 kg/m2 in Western populations and metabolic risks at BMI≥25 kg/m3 in Asian populations are recommended.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective:To investigate the clinical efficacy and safety of a baby smoothing and special caring cream in reducing the recurrence of atopic dermatitis (AD) in infancy.Methods:A randomized controlled trial was conducted. Children with moderate AD (with overall investigator's global assessment [IGA] scores of 3 - < 4) were enrolled from Shunyi Maternal and Children′s Hospital of Beijing Children′s Hospital from April 2021 to June 2024. During the induction period, all children were topically treated with 0.1% hydrocortisone butyrate cream twice daily on the lesional skin, as well as with a baby smoothing and special caring cream at least twice daily throughout the body; at the 2-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those with an IGA score of > 1 point continued the treatment for another 2 weeks; at the 4-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those still with an IGA score of > 1 point were withdrawn from the study, and received conventional treatment. Patients who entered the maintenance period were randomly divided into the test group and the control group in a 1∶1 ratio using a random number table. In the test group, the hydrocortisone butyrate cream was discontinued, while the baby smoothing and special caring cream was continued twice daily for 8 consecutive weeks; in the control group, both the hydrocortisone butyrate cream and the baby smoothing and special caring cream were discontinued. IGA and Scoring AD (SCORAD) scores were assessed by clinicians at weeks 4 and 8 in the maintenance phase, while the patient-oriented eczema measure (POEM) score was evaluated weekly by patients' parents. The Kaplan-Meier survival analysis and Breslow test were used to compare recurrence rates in the two groups (the primary efficacy outcome), and a generalized estimating equation model was used to evaluate the changes in IGA, SCORAD, and POEM scores in the two groups (the secondary efficacy outcomes). Adverse reactions were monitored throughout the study to evaluate safety.Results:A total of 68 children with moderate AD aged from 3 months to 2 years were included. There were 38 females and 30 males, aged 11.72 ± 6.03 months. Fifty-two patients entered the maintenance phase; 2 were lost to follow-up, and 50 were included in the per-protocol set, with 28 in the test group and 22 in the control group. The recurrence rate during the maintenance phase was 7.14% (2/28) in the test group and 31.82% (7/22) in the control group, showing a significant difference between the two groups ( χ 2 = 5.08, P = 0.032). At weeks 4 and 8 in the maintenance phase, the IGA scores were significantly lower in the test group than in the control group (Wald χ 2 = 5.06, P = 0.024), whereas the SCORAD scores showed no significant differences between the two groups (Wald χ 2 = 2.92, P = 0.087). During weeks 1 - 8 in the maintenance phase, the POEM scores showed no significant differences between the two groups or over time (both P > 0.05), while the two groups showed different change trends in POEM scores over time (Wald χ 2interaction = 55.37, Pinteraction < 0.001). Throughout the entire study period, no adverse reactions were observed among all 68 subjects. Conclusion:With a high safety profile, the baby smoothing and special caring cream could reduce the recurrence rate during the maintenance phase, showing promise as an adjuvant therapy for the maintenance treatment of AD in infancy, and is worthy of clinical application.