1.Transcutaneous bilirubin curves in healthy neonates based on multicenter remote monitoring data
Bi ZE ; Xiaoyue DONG ; Jin WANG ; Chuan NIE ; Jiajun ZHU ; Fang GUO ; Falin XU ; Chunhui YANG ; Bizhen SHI ; Zhankui LI ; Xinhua ZHANG ; Jing LI ; Bin YI ; Xiuying TIAN ; Lejia ZHANG ; Jun TANG ; Xinlin HOU ; Jiahua XU ; Guoying HUANG ; Shuping HAN ; Wenhao ZHOU
Chinese Journal of Pediatrics 2025;63(12):1318-1324
Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.
2.Transcutaneous bilirubin curves in healthy neonates based on multicenter remote monitoring data
Bi ZE ; Xiaoyue DONG ; Jin WANG ; Chuan NIE ; Jiajun ZHU ; Fang GUO ; Falin XU ; Chunhui YANG ; Bizhen SHI ; Zhankui LI ; Xinhua ZHANG ; Jing LI ; Bin YI ; Xiuying TIAN ; Lejia ZHANG ; Jun TANG ; Xinlin HOU ; Jiahua XU ; Guoying HUANG ; Shuping HAN ; Wenhao ZHOU
Chinese Journal of Pediatrics 2025;63(12):1318-1324
Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.
3.Discussion on the Optimal Dose of Aspirin in the Treatment of Acute Stage of Kawasaki’s Disease
Jie MI ; Zhuo LIU ; Yuan LI ; Yang LI ; Ziyun DUAN ; Wenwen ZHANG ; Jiahua LIU
Chinese Journal of Modern Applied Pharmacy 2024;41(3):386-390
OBJECTIVE
To study the effect of different doses of aspirin on clinical efficacy in acute stage of Kawasaki’s disease, and to explore the optimal dose of aspirin.
METHODS
A total of 150 patients suffered from Kawasaki’s disease were randomly selected by hospital information system from March to May 2022 for retrospective analysis. According to different doses of aspirin, they were divided into three groups: high dose group(>50 mg·kg−1·d−1), medium dose group(30−50 mg·kg−1·d−1) and low dose group(<30 mg·kg−1·d−1). The antipyretic time, the incidence of non-response to intravenous human immunoglobulin, the improvement of laboratory indexes and prevalence of adverse drug reaction were compared among the three groups.
RESULTS
There was no significant difference in body temperature recovery among the three groups under different doses of aspirin. There was no significant difference in patients with non-response to intravenous human immunoglobulin among the three groups. Before treatment, there were no significant differences in white blood cell(WBC) count, blood platelet(PLT) count and C-reactive protein(CRP) concentration among the three groups. After treatment, the count of WBC, PLT and CRP in the three groups was significantly improved compared with that before treatment, and the difference was statistically significant(P<0.05). However, there was no significant difference in the above indexes among the three groups after treatment. There was a higher incidence of adverse reactions in children treated with medium or high dose aspirin.
CONCLUSION
Different doses of aspirin combined with intravenous human immunoglobulin have good therapeutic effect on Kawasaki’s disease, but considering the safety and economy of aspirin, low dose administration is recommended.
4.The efficacy and safety of irreversible electroporation in the treatment of localized prostate cancer
Baijun DONG ; Jun YANG ; Yanqing WANG ; Haifeng WANG ; Jiahua PAN ; Shaogang WANG ; Wei XUE
Chinese Journal of Urology 2024;45(8):603-607
Objective:To investigate the efficacy and safety of irreversible electroporation in focal ablation of localized prostate cancer.Methods:Clinical data of 128 patients with localized prostate cancer treated with irreversible electroporation from August 2019 to September 2023 at Renji Hospital of Shanghai Jiaotong University School of Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Dongfang Hospital of Tongji University, were retrospectively analyzed. The median age was 68 (62, 75) years. The median PSA was 8.64 (5.83, 12.57) ng/ml. Gleason score was 6 in 57 cases, 7 in 39 cases, and greater than 7 in 19 cases. There were 4 cases of T 1c, 69 cases of T 2a, 27 cases of T 2b, and 28 cases of T 2c. No lymph node or distant metastasis was seen in preoperative examination. All patients had no preoperative urinary retention or urinary incontinence. Irreversible electroporation treatment was administered under general anesthesia with patients in the lithotomy position. A transrectal ultrasound probe was used to measure prostate lesion size, determining the type and number of electrode needles. Electrode needles were strategically positioned around the targeted lesion. The distance between each pair of needles used for ablation ranged from 0.5 to 2.0 cm. The system automatically generated treatment parameters, including voltage, current, and the number of pulses, with each pulse cycle lasting approximately 5 minutes. After treatment, the needles were removed, gauze was applied for 1 minute. The urethra was then irrigated with a painless iodine solution diluted 1∶1 with 0.9% saline, followed by the insertion of a urinary catheter. Treatment efficacy and adverse reactions were documented. Biochemical recurrence was defined as a PSA increase of over 2 ng/ml from the post-treatment nadir; imaging recurrence was identified by abnormal lesions on MRI or contrast-enhanced ultrasound. Results:All 128 surgeries were successfully completed. At 6 months postoperatively, 116 cases were followed. Tne median PSA was 1.58 (0.56, .95) ng/ml, which was 82.22% (65.37%, 93.33%) lower than preoperative level( P<0.01). Five patients (4.31%) had biochemical recurrence, and MRI or contrast-enhanced ultrasound examinations were negative, 1 patient underwent radical prostatectomy with pathology of prostate cancer, and the remaining 4 were continued to be followed up. Ninety-eight patients underwent MRI or contrast-enhanced ultrasound review, including 6 patients (6.12%) detected imaging recurrence, of which 2 patients underwent radical prostatectomy with pathology of prostate cancer, and the remaining 4 underwent endocrine therapy. The postoperative continence rate was 98.28%, and 8 patients (6.89%) had complications of class II. Conclusions:Irreversible electroporation for focal treatment of localized prostate cancer has shown favorable results in terms of tumor control, safety and urinary continence.
5.Clinical characteristics and prognosis of 69 immunocompetent patients with primary central nervous system lymphoma
Xiaojiao XU ; Jiahua ZHAO ; Xiaosa YANG ; Dongyang HU ; Rui LIU ; Tiantian ZHUANG ; Yubao MA ; Mianwang HE ; Fei YANG ; Jiatang ZHANG
Chinese Journal of Neuromedicine 2024;23(12):1225-1233
Objective:To explore the clinical features of immunocompetent primary central nervous system lymphoma (PCNSL) and influencing factors for prognosis of immunocompetent patients with PCNSL.Methods:A retrospective analysis was performed; 69 immunocompetent patients with PCNSL confirmed by pathology in First Medical Center of PLA General Hospital from January 2016 to January 2024 were enrolled; initial symptoms, Eastern Cooperative Oncology Group (ECOG) score, and results of laboratory and pathological examinations in these patients were collected. Patients were divided into biopsy confirmed group ( n=43) and lesion resection confirmed group ( n=26) according to different diagnostic methods; patients were also divided into chemotherapy group ( n=48), chemotherapy+radiotherapy group ( n=9) and surgical resection group ( n=12) according to different treatment methods. Clinical outcomes of these patients in different groups at the end of follow-up were compared, and the influencing factors for short-term prognosis (6 months after treatment) were identified. All patients were followed up for 12.80 (6.00, 36.40) months. The short-term prognosis was evaluated by modified Rankin scale (mRS) 6 months after treatment (mRS scores of 0-2: good prognosis; mRS scores of 3-6: poor prognosis). Overall survival (OS) was recorded at the end of follow-up. Results:Among the 69 immunocompetent patients with PCNSL, 37 were males and 32 were females; median onset age was 59 years, ranged 24-83 years. Focal neurologic deficits of different degrees (34/69, limb weakness, sensory disturbances, ataxia, or eye involvement) were the most common initial symptoms, followed by headache (14/69), dizziness (10/69), cognitive dysfunction (9/69), epilepsy (1/69) and psychiatric disorders (1/69). Forty-five patients underwent cerebrospinal fluid examination: 17 had cerebrospinal fluid pressure≥200 mmH 2O (1 mmH 2O=9.8 Pa); 10 had increased white blood cell count (>10×10 6/L), reaching to (16.5[11.0, 20.0])×10 6/L; 32 had increased protein level, reaching to 758.10 (547.83, 948.13) mg/L. Cerebrospinal fluid cytology was performed in 15 patients, and tumor cells were found in only 1 patient. Cranial MRI showed that intracranial solitary lesions were more common (60.87%, 42/69), and most lesions were at the basal ganglia region (40.58%, 28/69). PET/CT showed a obviously higher metabolism of the lesions (97.06, 33/34), with maximum standardized uptake of 22.9 (13.9, 30.55) g/mL. All patients had diffuse large B-cell lymphoma (DLBCL). By the end of follow-up, 28 patients died. Logistic regression analysis showed that ECOG score≥2 ( OR=9.210, 95% CI: 2.558-32.896, P=0.001) and positive MYC ( OR=0.088, 95% CI: 0.008-0.973, P=0.047) were independent risk factors for poor short-term prognosis. Cox proportional hazard regression model analysis showed that ECOG score≥2 ( HR=5.135, 95% CI: 2.230-11.827, P<0.001), positive B-cell lymphoma 6 (BCL-6, HR=0.226, 95% CI: 0.079-0.649, P=0.006) and chemotherapy or chemotherapy+radiotherapy ( HR=0.392, 95% CI: 0.157-0.980, P=0.045) were independent prognostic factors for OS. Conclusions:In immunocompetent patients with PCNSL, focal neurological deficits are more common at the onset, and fever is rare. Patients with ECOG score≥2 are more likely to have poor short-term prognosis and short OS. MYC-positive patients will have a better short-term prognosis; BCL-6 positive patients and patients treated with chemotherapy or chemotherapy+radiotherapy will have longer OS.
6.Clinical characteristics and prognosis of 69 immunocompetent patients with primary central nervous system lymphoma
Xiaojiao XU ; Jiahua ZHAO ; Xiaosa YANG ; Dongyang HU ; Rui LIU ; Tiantian ZHUANG ; Yubao MA ; Mianwang HE ; Fei YANG ; Jiatang ZHANG
Chinese Journal of Neuromedicine 2024;23(12):1225-1233
Objective:To explore the clinical features of immunocompetent primary central nervous system lymphoma (PCNSL) and influencing factors for prognosis of immunocompetent patients with PCNSL.Methods:A retrospective analysis was performed; 69 immunocompetent patients with PCNSL confirmed by pathology in First Medical Center of PLA General Hospital from January 2016 to January 2024 were enrolled; initial symptoms, Eastern Cooperative Oncology Group (ECOG) score, and results of laboratory and pathological examinations in these patients were collected. Patients were divided into biopsy confirmed group ( n=43) and lesion resection confirmed group ( n=26) according to different diagnostic methods; patients were also divided into chemotherapy group ( n=48), chemotherapy+radiotherapy group ( n=9) and surgical resection group ( n=12) according to different treatment methods. Clinical outcomes of these patients in different groups at the end of follow-up were compared, and the influencing factors for short-term prognosis (6 months after treatment) were identified. All patients were followed up for 12.80 (6.00, 36.40) months. The short-term prognosis was evaluated by modified Rankin scale (mRS) 6 months after treatment (mRS scores of 0-2: good prognosis; mRS scores of 3-6: poor prognosis). Overall survival (OS) was recorded at the end of follow-up. Results:Among the 69 immunocompetent patients with PCNSL, 37 were males and 32 were females; median onset age was 59 years, ranged 24-83 years. Focal neurologic deficits of different degrees (34/69, limb weakness, sensory disturbances, ataxia, or eye involvement) were the most common initial symptoms, followed by headache (14/69), dizziness (10/69), cognitive dysfunction (9/69), epilepsy (1/69) and psychiatric disorders (1/69). Forty-five patients underwent cerebrospinal fluid examination: 17 had cerebrospinal fluid pressure≥200 mmH 2O (1 mmH 2O=9.8 Pa); 10 had increased white blood cell count (>10×10 6/L), reaching to (16.5[11.0, 20.0])×10 6/L; 32 had increased protein level, reaching to 758.10 (547.83, 948.13) mg/L. Cerebrospinal fluid cytology was performed in 15 patients, and tumor cells were found in only 1 patient. Cranial MRI showed that intracranial solitary lesions were more common (60.87%, 42/69), and most lesions were at the basal ganglia region (40.58%, 28/69). PET/CT showed a obviously higher metabolism of the lesions (97.06, 33/34), with maximum standardized uptake of 22.9 (13.9, 30.55) g/mL. All patients had diffuse large B-cell lymphoma (DLBCL). By the end of follow-up, 28 patients died. Logistic regression analysis showed that ECOG score≥2 ( OR=9.210, 95% CI: 2.558-32.896, P=0.001) and positive MYC ( OR=0.088, 95% CI: 0.008-0.973, P=0.047) were independent risk factors for poor short-term prognosis. Cox proportional hazard regression model analysis showed that ECOG score≥2 ( HR=5.135, 95% CI: 2.230-11.827, P<0.001), positive B-cell lymphoma 6 (BCL-6, HR=0.226, 95% CI: 0.079-0.649, P=0.006) and chemotherapy or chemotherapy+radiotherapy ( HR=0.392, 95% CI: 0.157-0.980, P=0.045) were independent prognostic factors for OS. Conclusions:In immunocompetent patients with PCNSL, focal neurological deficits are more common at the onset, and fever is rare. Patients with ECOG score≥2 are more likely to have poor short-term prognosis and short OS. MYC-positive patients will have a better short-term prognosis; BCL-6 positive patients and patients treated with chemotherapy or chemotherapy+radiotherapy will have longer OS.
7.Heart sound classification algorithm based on time-frequency combination feature and adaptive fuzzy neural network.
Qin WANG ; Hongbo YANG ; Jiahua PAN ; Yingjie TIAN ; Tao GUO ; Weilian WANG
Journal of Biomedical Engineering 2023;40(6):1152-1159
Feature extraction methods and classifier selection are two critical steps in heart sound classification. To capture the pathological features of heart sound signals, this paper introduces a feature extraction method that combines mel-frequency cepstral coefficients (MFCC) and power spectral density (PSD). Unlike conventional classifiers, the adaptive neuro-fuzzy inference system (ANFIS) was chosen as the classifier for this study. In terms of experimental design, we compared different PSDs across various time intervals and frequency ranges, selecting the characteristics with the most effective classification outcomes. We compared four statistical properties, including mean PSD, standard deviation PSD, variance PSD, and median PSD. Through experimental comparisons, we found that combining the features of median PSD and MFCC with heart sound systolic period of 100-300 Hz yielded the best results. The accuracy, precision, sensitivity, specificity, and F1 score were determined to be 96.50%, 99.27%, 93.35%, 99.60%, and 96.35%, respectively. These results demonstrate the algorithm's significant potential for aiding in the diagnosis of congenital heart disease.
Humans
;
Heart Sounds
;
Neural Networks, Computer
;
Algorithms
;
Heart Defects, Congenital
8.Incision scar recovery assessment of patients with transaxillary dual-plane breast augmentation assisted with endoscopy
Juan AN ; Huai'an LIN ; Yifan ZHANG ; Jiahua HU ; Yang YU ; Jiaming SUN ; Zhaohao ZHONG ; Danning ZHENG ; Li YU
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(3):167-170
Objective:To evaluate incision scars of transaxillary breast augmentation by different methods of scar assessment.Methods:A retrospective study was carried out on 30 patients (age range 20 to 50 years, with mean age of 32 years) who underwent endoscopic assisted transaxillary type Ⅰ dual plane breast implant augmentation by a same surgeon from August 2014 to November 2016. Scars were estimated by 3 methods which included Vancouver Scar Scale (VSS), Visual Assessment Scale (VAS) and patients' questionnaire.Results:VAS score for left side scars ranged from 0 to 8 and the median was 1. VAS score for right side scars ranged from 0 to 8.3 and the median was 1. A total of 48 scars were scored in the 0-2 point range, representing 80% of the 60 total. VSS score for left side scars ranged from 0 to 11.6 and the median was 0.8. VSS score for right side scars ranged from 0 to 11.3 and the median was 1.2. A total of 46 scars were scored in the 0-2 point range, representing 76.7% of the total 60 breats. The scores between VSS and VAS had significant statistical differences ( P<0.001). 80.0% of our patients regarded scars as unconspicuous or basically invisible in our questionnaire. Conclusions:The majority of transaxillary incision scars recover in favorable status with high patients satisfactory rate. VAS is a practical tool for evaluating transaxillary incision scars. The VSS score is not equivalent to the VAS score when grading scars only by photos.
9.Effect of couch rotation angle on non-coplanar static intensity-modulated radiotherapy plan for gastric cancer
Jiping WANG ; Guodong YANG ; Jiahua ZOU ; Zhiyong YANG
Chinese Journal of Radiological Health 2023;32(5):542-549
Objective To investigate the effect of couch rotation angle on non-coplanar static intensity-modulated radiotherapy (IMRT) plan for gastric cancer and to provide a reference for clinical planning. Methods A retrospective analysis was conducted on patients who recently underwent postoperative IMRT for gastric cancer. Twenty patients who received radiotherapy in the centre of Radiation Oncology of Huanggang Central Hospital from August 2022 to January 2023 were selected. That were selected to receive a seven-field coplanar static IMRT plan based on a couch rotation angle of 0° as the control group. Then, based on the coplanar IMRT plan, only the couch rotation angle of gantry angles 30° and 330° was changed to 10°, 20°, 30°, 40°, 50°, 60°, 70°, 80°, and 90°, respectively, and nine different non-coplanar plans were established. The homogeneity index (HI), conformity index (CI) of the target volume, and monitor unit (MU), as well as Dmean, V20, and V30 of the left and right kidneys, Dmax, Dmean, V10, V20, and V30 of the spinal cord, and Dmax, Dmean, V10, V20, V30, and V40 of the small intestine and liver were compared among the 10 plans. The MU and the dosimetric parameters of the target volumes and When the couch rotation angle was 60°, the minimum HI and maximum CI of the target volume were 0.0714±0.0089 and 0.9271±0.0108, respectively, and the minimum MU was 438±26, with the best homogeneity and conformity in the target volume and the shortest machine treatment time (P<0.05). When the couch rotation angle was 10°, the Dmax of the small intestine was lowest, being (4620.73±99.27) cGy. When the couch rotation angle was 60°, the Dmean of the left and right kidneys was lowest, being (1246.30±130.35) cGy and (1001.52±103.33) cGy, respectively; the V20 of the left and right kidneys was lowest, being 22.87±6.29 and 19.69±1.84, respectively; the V10 and V30 of the spinal cord were lowest, being 40.08±4.92 and 1.68±0.34, respectively (P<0.05). Conclusion The couch rotation angle has some influence on the postoperative treatment planning for patients with gastric cancer. In the design of non-coplanar plan for gastric cancer, the couch rotation angle of 60° contributes to establishing a better radiotherapy plan.
10.Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy.
Jianjun CHENG ; Haitian ZHAO ; Bin LI ; Hua ZHANG ; Qianyu ZHAO ; Shiyao FU ; Ying HAN ; Weihong LU ; Jiahua SHI ; Xin YANG
Acta Pharmaceutica Sinica B 2023;13(2):879-896
Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.


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