Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To explore the trajectory and influencing factors of oral frailty in first-onset elderly patients with ischemic stroke.Methods:A total of 240 inpatients from the neurology departments of Wutaishan Hospital and Northern Jiangsu People's Hospital between October 2022 and February 2024 were selected by convenience sampling. Oral frailty scores were assessed dynamically at four time points: 1 day before discharge (T 1) , 1 month after discharge (T 2) , 3 months after discharge (T 3) , and 6 months after discharge (T 4) . Latent growth modeling was used to identify potential trajectory categories and analyze their influencing factors. Results:A total of 240 questionnaires were distributed, with 220 valid responses, yielding a response rate of 91.67%. A total of three trajectory types of oral frailty were identified: non-oral frailty group ( n=92) , low-decline group ( n=66) , and high-decline group ( n=62) . Age, marital status, smoking history, dysphagia, National Institute of Health Stroke Scale score, oral health, nutritional status, oral health-related self-efficacy, monthly per capita household income, polypharmacy, denture use, and cognitive function were influencing factors of oral frailty in first-onset elderly patients with ischemic stroke ( P<0.05) . Conclusions:From 1 day before discharge to 6 months after discharge, there are 3 distinct oral frailty trajectories in first-onset elderly patients with ischemic stroke. Medical staff should implement individualized interventions based on the identified influencing factors.

Objective:To explore the trajectory and influencing factors of oral frailty in first-onset elderly patients with ischemic stroke.Methods:A total of 240 inpatients from the neurology departments of Wutaishan Hospital and Northern Jiangsu People's Hospital between October 2022 and February 2024 were selected by convenience sampling. Oral frailty scores were assessed dynamically at four time points: 1 day before discharge (T 1) , 1 month after discharge (T 2) , 3 months after discharge (T 3) , and 6 months after discharge (T 4) . Latent growth modeling was used to identify potential trajectory categories and analyze their influencing factors. Results:A total of 240 questionnaires were distributed, with 220 valid responses, yielding a response rate of 91.67%. A total of three trajectory types of oral frailty were identified: non-oral frailty group ( n=92) , low-decline group ( n=66) , and high-decline group ( n=62) . Age, marital status, smoking history, dysphagia, National Institute of Health Stroke Scale score, oral health, nutritional status, oral health-related self-efficacy, monthly per capita household income, polypharmacy, denture use, and cognitive function were influencing factors of oral frailty in first-onset elderly patients with ischemic stroke ( P<0.05) . Conclusions:From 1 day before discharge to 6 months after discharge, there are 3 distinct oral frailty trajectories in first-onset elderly patients with ischemic stroke. Medical staff should implement individualized interventions based on the identified influencing factors.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

This article presents a case study of a patient who had Cronkhite-Canada syndrome in combination with an asymptomatic novel coronavirus infection. The patient exhibited clinical symptoms of loss of appetite, hair and nail loss, and skin pigmentation. Digestive endoscopy revealed widespread and varying-sized polypoid changes in the mucosa of the stomach, duodenum, and colon. During the course of the illness, the patient tested positive for novel coronavirus nucleic acid. Treatment with moderate doses of prednisone resulted in the patient's hair regrowth and decreased skin hypopigmentation. The article provides a summary of the patient's diagnosis and treatment and a review of relevant literature, with the aim of enhancing clinicians' understanding of the disease.

Objective: To evaluate the effectiveness of craniocervical flexion training using pressure biofeedback combined with cervical traction among patients with cervical spondylotic radiculopathy (CSR). Methods: Sixty patients with CSR receiving treatment in Center of Rehabilitation, Zhejiang Hospital from January 2020 to December 2021 were enrolled and randomly assigned into the control and treatment groups, of 30 patients in each group. All patients were given cervical traction, and patients in the treatment group were given additional craniocervical flexion training using pressure biofeedback for successive four weeks. The effectiveness of craniocervical flexion training combined with cervical traction was evaluated using Visual Analogue Scale (VAS), Neck Disability Index (NDI) and the active range of motion (AROM) of cervical flexion, and the neck pain and cervical functions were compared between the two groups before and after treatments using repeated-measures analysis of variance. Results: Fifteen men were included in the treatment group, with a mean age of (49.47±5.33) years, mean disease course of (5.53±2.89) months, and mean VAS score of (4.73±1.39) points, and there were no significant differences between the control and treatment groups in terms of gender, age, course of disease or VAS score (P>0.05). The VAS score and NDI were lower 4 weeks post-treatment than pretreatment in both the treatment [VAS score: (2.13±1.01) vs. (4.73±1.39); NDI: (12.17±2.12) vs. (20.20±3.78)] and control groups [VAS score: (2.93±1.11) vs. (4.90±1.21); NDI: (15.23±2.39) vs. (19.60±3.30)], and the AROM of cervical flexion was significantly higher 4 weeks post-treatment than pretreatment in both the treatment [(42.87°±2.99°) vs. (37.50°±2.80°)] and control groups [(41.80°±3.61°) vs. (38.07°±2.99°)]; there was an interaction between time and group, and a higher improvement for cervical functions was seen in the treatment group than in the control group (FVAS =5.119, P=0.027; FNDI=15.473, P<0.001; FAROM=11.443, P<0.001). Conclusion Craniocervical flexion training using pressure biofeedback combined with cervical traction may effectively alleviate the neck pain and increase the AROM among patients with CRS, which is more effective to improve patients' cervical functions than cervical traction alone.

Objective     To summarize the surgical treatment experience in neonates with coarctation of the aorta (CoA) and aortic arch hypoplasia (AAH). Methods     The neonates with CoA and AAH who underwent surgical treatment in the Department of Pediatric Cardiac Surgery of Guangdong Provincial People's Hospital from 2013 to 2020 were retrospectively enrolled. The postoperative complications, long-term survival rate, and freedom from aortic reobstruction were analyzed. Patients undergoing extended end-to-end anastomosis were allocated into an extended end-to-end group, those undergoing extended end-to-side anastomosis into an extended end-to-side group, and those undergoing pulmonary autograft patch aortoplasty into a patch aortoplasty group. Results     Finally 44 patients were  enrolled, including 37 males and 7 females, aged 5.00-30.00 (19.34±7.61) days and weighted 2.00-4.50 (3.30±0.60) kg. There were 19 patients of extended end-to-end anastomosis, 19 patients of extended end-to-side anastomosis, and 6 patients of pulmonary autograft patch aortoplasty. The mean values of the Z scores of the proximal, distal, and isthmus of the aortic arch were –2.91±1.52, –3.40±1.30, and –4.04±1.98, respectively. The mean follow-up time was 45.6±3.7 months. There were 2 early deaths and no late deaths. Aortic reobstruction occurred in 8 patients, and 3 patients underwent reoperation intervention. The 5-year rate of freedom from reobstruction was 78.8%. The Cox multivariable regression analysis showed that the related factors for postoperative reobstruction were the Z score of the preoperative proximal aortic arch (HR=0.152, 95%CI 0.038-0.601, P=0.007) and the postoperative left main bronchus compression (HR=15.261, 95%CI 1.104-210.978, P=0.042). Conclusion     Three surgical procedures for neonates with CoA and AAH are safe and effective, but the aortic reobstruction rate in long term is not low. The smaller Z score of the preoperative proximal aortic arch and the postoperative left main bronchus compression are risk factors for long-term aortic reobstruction.

Objective    To characterize surgical outcomes of supra-cardiac total anomalous pulmonary venous connection (TAPVC), investigate risk factors for postoperative death, and explore informed LASSO machine learning methods to solve "small sample size problem" in research of rare congenital heart diseases. Methods    A retrospective analysis of 241 patients with supra-cardiac TAPVC who underwent surgical repair in Guangdong Provincial People's Hospital from 2009 to 2019 was conducted, including 179 males and 62 females with a median surgical age of 71 (33, 232) d. Detailed clinical data of the postoperative death-related factors were extracted. Univariable Cox proportional hazard models were used to initially screen potential risk factors for postoperative death. Factors with P鈮?.05 were retained. To solve the limitation of small sample size and the "P>n" problem, we proposed a novel LASSO method for conducting multivariable Cox regression analysis that was capable of bringing in findings of related studies to improve analysis power and to reduce false-negative findings. Results 聽 聽Univariable Cox analyses showed several potential clinical risk factors, among which highly significant factors (P<0.001) included: surgical weight鈮?.5 kg (HR=16.00), main pulmonary artery diameter (HR=0.78), prolonged cardiopulmonary bypass time (HR=1.21), aortic block time (HR=1.28), and postoperative ventilator-assisted time (HR=1.13/d). LASSO multivariable analysis revealed that independent risk factors for postoperative death included cardiopulmonary bypass time (aHR=1.308/30 min), age (aHR=0.898), postoperative ventilator-assisted time (aHR=1.023/d), weight鈮?.5 kg (aHR=2.545), right vertical venous return (aHR=1.977), preoperative pulmonary venous obstruction (aHR=1.633) and emergency surgery (aHR=1.383). Conclusion 聽 聽Our proposed informed LASSO method can use previous studies' results to improve the power of analysis and effectively solve the "P>n" and small sample size limitation. Cardiopulmonary bypass time, surgical age, postoperative ventilator-assisted time, weight, right vertical venous return, preoperative pulmonary venous obstruction, and emergency surgery are risk factors for postoperative death of supra-cardiac TAPVC.