Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

OBJECTIVE: To investigate the clinical effect of subchondral blocking technique combined with plate and screw biplane fixation in the treatment of complex acetabular posterior wall fractures. METHODS: From July 2015 to December 2019, a total of 47 cases of acetabular posterior wall fractures were treated. According to the different internal fixation techniques, they were divided into the external blocking fixation group supported by lateral plate and screw(control group of 23 cases) and the subchondral blocking technique combined with lateral plate and screw support biplane fixation group(study group of 24 cases). In the control group, there were 15 males and 8 females, aged 18 to 68 years old with an average of (40.9±7.2) years;preoperative preparation was 4 to 13 days with an average of (7.9±1.5) days. In the study group, there were 14 males and 10 females, aged 20 to 71 years old with an average of (41.7±7.9) years;preoperative preparation was 4 to 12 days with an average of (7.5±1.9) days. Kocher-Langenbeck approach was used in both groups and all patients were followed up for at least 1 year. The operation time, intraoperative blood loss, hospitalization time, quality of fracture reduction after operation, modified Merle D'Aubigne Postel score of hip joint one year after operation and postoperative complication rate of two groups were statistically analyzed and compared. RESULTS: The patients in both groups were followed up for at least 1 year. One year after operation, the Merled'Aubigne Postel score(16.042±1.517) of hip function improvement in the study group was significantly higher than that in the control group (14.696±1.222)(P<0.05). There was no significant difference in operation time and intraoperative bleeding between the two groups(P>0.05). One year after operation, there was a significant difference between two groups in the evaluation results of Matta fracture reduction quality(P<0.05). There was no significant difference in postoperative complications between two groups(P>0.05). CONCLUSION The treatment of complex acetabular posterior wall fracture with subchondral blocking technique combined with plate and screw biplane fixation technique has lower postoperative complication rate, better functional recovery of hip joint and satisfactory clinical effect.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Acetabulum/injuries* ; Bone Screws ; Hip Fractures/surgery* ; Spinal Fractures ; Treatment Outcome ; Postoperative Complications

OBJECTIVE: To assess the clinical efficacy of minimally invasive technology with trajectory screw fixation for fragility fractures of pelvic(FFP). METHODS: A retrospective case control study was performed to analyze the clinical data of 35 patients with FFP who were treated and followed up between January 2016 and December 2019. There were 12 males and 23 females, aged from 65 to 99 years with an average of(75.4±7.8) years old. There were 13 cases of type Ⅱb, 7 cases of type Ⅱc, 8 cases of type Ⅲa, 2 cases of type Ⅲb, 2 cases of type Ⅲc, 1 case of type Ⅳb, and 2 cases of type Ⅳc according to Rommens FFP comprehensive classification. All patients received the treatment of minimally invasive technology with trajectory screws fixation. According to the different methods of anterior pelvic ring fixation, FFP patients were divided into two groups:12 cases were fixed with the pedicle screw rod system in the anterior pelvic subcutaneous internal fixator (INFIX) group;23 cases were fixed with hollow screws of the pubic symphysis, superior ramus of pubis or acetabular anterior column in the screw group. The operation time, intraoperative blood loss, intraoperative fluoroscopy times, length of hospital stay, cost of internal fixation, pre- and post-operative visual analogue scale(VAS) were compared between the two groups. The fracture reduction quality was evaluated according to the Matta criteria, and the clinical function was evaluated by the Majeed functional scoring system respectively. RESULTS: All patients were followed up for 12 to 39(16.5±5.4) months after surgery. There was no statistically significant difference in the operation time, intraoperative blood loss, intraoperative fluoroscopy time, and length of hospital stay between the two groups(P>0.05). As for the cost of internal fixation, the cost of internal fixation in the screw group [2 914 (2 914, 4 371) yuan] was significantly lower than that of the INFIX group [6 205 (6 205, 6 205) yuan] (P<0.05). No significant difference was observed in the incidence of postoperative complications between the two groups (P>0.05). There was no significant difference in VAS assessment at admission, 1 week, and 3 months after surgery between the two groups(P>0.05). However, the VAS assessment at 1 week and 3 months after surgery of the two groups were significantly better than those at admission(P<0.05). There was no significant difference in the quality of fracture reduction after the operation and the efficacy evaluation at the last follow-up between the two groups(P>0.05). CONCLUSION For the treatment of fragility fractures, minimally invasive technology with trajectory screw fixation can achieve good clinical efficacy. It has the advantages of being relatively minimally invasive, less bleeding, relieving the pain. It deserves clinical application.
Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Case-Control Studies ; Female ; Fractures, Bone/surgery* ; Humans ; Male ; Pelvic Bones/surgery* ; Retrospective Studies

OBJECTIVES: To examine the association between duration of fever before intravenous immunoglobulin (IVIG) treatment and IVIG resistance in children with Kawasaki disease (KD). METHODS: A retrospective analysis was performed on the medical data of 317 children with KD who were admitted from January 2018 to December 2020. According to the duration of fever before IVIG treatment, they were divided into two groups: short fever duration group (≤4 days) with 92 children and long fever duration group (>4 days) with 225 children. According to the presence or absence of IVIG resistance, each group was further divided into a drug-resistance group and a non-drug-resistance group. Baseline data and laboratory results were compared between groups. A multivariate logistic regression analysis was used to identify the influencing factors for IVIG resistance. RESULTS: In the short fever duration group, 19 children (20.7%) had IVIG resistance and 5 children (5.4%) had coronary artery aneurysm, and in the long fever duration group, 22 children (9.8%) had IVIG resistance and 19 children (8.4%) had coronary artery aneurysm, suggesting that the short fever duration group had a significantly higher rate of IVIG resistance than the long fever duration group (P<0.05), while there was no significant difference in the incidence rate of coronary artery aneurysm between the two groups (P>0.05). In the short fever duration group, compared with the children without drug resistance, the children with drug resistance had a significantly lower level of blood sodium and significantly higher levels of procalcitonin, C-reactive protein, and N-terminal B-type natriuretic peptide before treatment (P<0.05). In the long fever duration group, the children with drug resistance had significantly lower levels of blood sodium and creatine kinase before treatment than those without drug resistance (P<0.05). The multivariate logistic regression analysis showed that a reduction in blood sodium level was associated with IVIG resistance in the long fever duration group (P<0.05). CONCLUSIONS IVIG resistance in children with KD varies with the duration of fever before treatment. A reduction in blood sodium is associated with IVIG resistance in KD children with a duration of fever of >4 days before treatment.
Child ; Coronary Aneurysm/drug therapy* ; Fever/etiology* ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Infant ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies ; Sodium/therapeutic use*

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

Objective To explore the effect of imiquimod (IMQ) on the proliferation of glioma U87 cell line U87. Methods U87 cells were divided into control group, 1 mmol/L I mmol/L MQ group, 5 mmol/L IMQ group, 1 mmol/L IMQ+ STAT3 inhibitor(STAT3-IN) group and 5 mmol/L IMQ + STAT3-IN group. To detect the number of 5-ethynyl-2 ' - deoxyuridine(EdU) -labeled cells or proliferation absorbance(A) values in each group by EdU and MTT assays. Interleukin (I L) - 6 mRNA, tumor necrosis factor (TNF) -a mRNA and protein content in U87 cells of each group were detected by Real-time PCR or ELISA. Western blotting was used to detect the protein expression of STAT3, phosphorylated STAT3 (p - S T A T 3), nuclear factor (N F) -KB and phosphorylated NF-KB (p-NF-KB) in U87 cells of each group. Results Compared with the control group, the number of EdU-labeled cells and absorbance values of U87 cells were successively decreased in 1 mmol/L IMQ group and 5 mmol/L IMQ group, showing a dose-dependent manner (P < 0 . 0 1, n— 1 0) . However, the number of EdU-labeled cells and the A values in IMQ + STAT3-IN group and 5 mmol/L IMQ + STAT3-IN group were significantly reduced. Compared with the control group, the protein expression of STAT3, p-STAT3, N F - K B, P ~ N F - K B, IL-6 and TNF-a were continuing low level in U87 cells of 1 mmol/L IMQ group and 5 mmol/L IMQ group (P < 0 . 0 1, * = 1 0) . As well as in 1 mmol/L IMQ + STAT3-INgroup and 5 mmol/L IMQ + STAT3-IN group, the proteins of above were low expressed (P < 0 . 01, n— 10) . Conclusion Imiquimod decreased the contents of IL-6 and TNF-a by down-regulating S T A T 3 / N F - K B pathway, and thus inhibited the proliferation of U87 cells.

OBJECTIVE: To evaluate the efficacy of iliolumbar fixation in the treatment of U-shaped sacral fractures. METHODS: A retrospective study was conducted on the 14 complex U-shaped sacral fractures which had been treated from January 2014 to December 2019, involved 10 males and 4 females, aged 24 to 48 (35.4±6.5) years. Fracture healing time, nerve function, clinical function and complications were observed in the patients. RESULTS: All patients were followed up for 9 to 16(26.0±5.9) months. The complete weight-bearing time for bone healing was(12.4±2.0) weeks. One case of surgical incision infection occurred after operation, and one case of sacrum nailspenetrated to the outer plate of sacrum. No complications such as pressure ulcers, loosening or rupture of internal fixation occurred. According to Gibbons scoring, the neurological function recovered from preoperative 2.9±0.9 to postoperative 2.1±1.1, there were statistically significant differences between preoperative and postoperative ( CONCLUSION Sacral lumbar fixation is an effective method for the treatment of U-shaped sacrum fractures. It has the advantages of strong internal fixation and satisfactory functional recovery.
Bone Screws ; Female ; Fracture Fixation, Internal ; Humans ; Male ; Retrospective Studies ; Sacrum/surgery* ; Spinal Fractures/surgery* ; Treatment Outcome

Objective::To study the effect of total alkaloids of Nandina domestica in attenuating arsenic trioxide, and analyze chemical constituents of alkaloids extract of Nandina, in order to provide the theoretical basis for studying the effect of N. domestica in attenuating arsenic trioxide with alkaloids extract of N. domestica as effective fraction. Method::The model of acute liver injury induced by arsenic trioxide was used to compare the effects on heart and liver functions of mice between arsenic trioxide alone and total alkaloids of N. domestica combined with arsenic trioxide. The detoxification of total alkaloids on arsenic trioxide was evaluated based on biochemical parameters and pathological report. Peakview (Version1.2, AB SCIEX) software was used to process the mass spectrometry data of total alkaloids of N. domestica. The structures of determined compounds were identified by molecular weight of compound (molecular formula), secondary fragments, chromatographic peak retention and literature information. Result::Among biochemical indicators, creatine kinase(CK), lactate dehydrogenase(LDH), blood urea nitrogen(BUN), malondialdehyde(MDA), alanine aminotransferase(ALT) and amino transferase of aspartate(AST) of the arsenic trioxide group were increased, while elimination rates of Na⁺ -K⁺ -adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and serum creatinine(SCr) were decreased, compared with those of the combination group. CK and LDH of the alkaloids extract group were more obviously increased than those of the N. domestica extract group, but with no remarkable difference. In histomorphometric examination, edema of mouse heart cells was improved, and some kidney and liver damages in rats were alleviated. Totally 25 alkaloids of alkaloid extract were identified. Among them, 18 were known, and 7 were unknown, including 3 structural types, in which apomorphine alkaloids were mostly. Conclusion::Heart, kidney and liver damage degrees of the combination group were significantly alleviated compared with the arsenic trioxide group. The total alkaloids fraction extracted and purified have a significant attenuation in arsenic trioxide toxicity. The detoxification of total alkaloids extract was equal to that of N. domestica extract. Furthermore, apomorphine alkaloids, such as nantenine and domesticine, can be used as index components to establish a quality control method for total alkaloids.