The debate on the merits of proton radiotherapy and photon radiotherapy has lasted for more than 20 years, mainly reflected in the comparison of dose distribution and clinical outcomes. Because dosimetric advantages do not always translate to better clinical outcomes, several phase Ⅲ comparative clinical studies are being conducted in Western countries. However, it is highly questionable that these studies will bring great value to the advancement of radiation therapy or settle the debate. This is because the effectiveness of the treatment depends not only on the type of radiation, but also on the technology used. Therefore, the focus of the research should not be which type of radiation is superior, but how to avoid its disadvantages while taking full advantage of the dose characteristics of each type of radiation. Both proton therapy and photon therapy will play an important role in cancer treatment in the future, and limited resources should be applied to maximize the effectiveness of each. With the rapid development of radiotherapy technology and systemic therapies including immunotherapy, reducing treatment fractions in the form of stereotactic radiosurgery and stereotactic body radiotherapy (SRS/SBRT) will be the inevitable trend. The need for dose focusing will drive photon therapy toward 4π radiotherapy using more non-coplanar fields, while higher geometric accuracy requirements will cause wide adoption of artificial intelligence-based online adaptive radiotherapy.

Objective To analyze the anesthetic effect and hemodynamic impact of oxybutynin(OBI)combined with dexmedetomidine(DEX)on patients undergoing endoscopic dacryocystorhinostomy(En-DCR).Methods Patients who underwent En-DCR from February 2024 to May 2024 at Mianyang Wanjiang Eye Hospital were recruited.They were randomly divided into the DEX group(DEX administration only)and the combined group(DEX combined with OLI administration)according to the random number table method.The primary observational index in this study was the 24-h postoperative pain numerical rating scale(NRS)scores.The secondary observation indexes were heart rate(HR),mean arterial pressure(MAP),respiratory recovery time(SRT),extubation time(ET)and awakening time(AT),peak systolic value(PSV),end-diastolic blood flow velocity(EDV),resistance index(RI)and blood flow(BF).The occurrence of adverse events in patients during hospitalization was observed and recorded.Results A total of 80 patients were included in the study,with 40 in each of the DEX group and the combined group.In terms of analgesia,the NRS scores in the combined group were lower than those in the DEX group at T1(within 0.5 h after catheter removal),T2(4 h postoperatively),T3(8 h postoperatively),and T4(24 h postoperatively)(P＜0.05),and the remedial analgesia rate in the combined group was significantly lower than that in the DEX group(P＜0.05).Regarding anesthetic effects,HR and MAP at time points T6(during induction of anesthesia),T7(intraoperatively)and T8(during resuscitation)were lower in the combined group than in the DEX group(P＜0.05);and SRT,ET and AT were shorter in the combined group compared with the DEX group(P＜0.05).In terms of hemodynamics,at 24 h postoperatively,PSV,EDV and BF were significantly higher in both groups compared with those before anesthesia,whereas RI was significantly lower than before anesthesia(P＜0.05);PSV,EDV and BF were higher in the combined group than those in the DEX group,and RI was lower than that in the DEX group(P＜0.05).Regarding adverse reactions,the incidence of adverse reactions in the combined group was significantly lower than that in the DEX group(P＜0.05).Conclusion OLI combined with DEX prophylactic analgesia for patients with En-DCR is effective,not only to reduce postoperative pain,stabilize hemodynamics,shorten the time of extubation and awakening,and reduce the incidence of adverse reactions.

Objective:To explore the clinical efficacy of apatinib combined with tirelizumab in the treatment of advanced gastric cancer patients who failed first-line chemotherapy, as well as its impact on peripheral blood tumor angiogenesis regulatory factor levels and long-term survival.Methods:A prospective study was conducted on 144 advanced gastric cancer patients who failed first-line chemotherapy and were admitted to the Handan Central Hospital from January 2020 to December 2021. They were divided into two groups using a random number table method, with 72 patients in each group. The control group was treated with tirezizumab alone, while the observation group was treated with apatinib combined with tirezizumab. After four consecutive courses of treatment, the short-term efficacy of both groups was observed. We compared the levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA724, CA125], tumor angiogenesis regulatory factors [vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1 α), insulin-like growth factor-1 (IGF-1), matrix metalloproteinase-9 (MMP-9)], and quality of life scores between two groups before and after treatment. Long term follow-up was conducted on all patients, and the long-term survival status of two groups was statistically analyzed. Two groups of adverse reactions were compared.Results:The objective remission rate and disease control rate (51.39%, 80.56%) of the observation group were significantly higher than those of the control group (31.94%, 61.11%, all P<0.05). After treatment, the serum levels of CEA, CA199, CA724, CA125, VEGF, SDF-1α, IGF-1, and MMP-9 in both groups were significantly reduced compared with those before treatment (all P<0.05), and the observed group showed a more significant decrease in the above indicators (all P<0.05). After treatment, the scores of physical function, emotional function, social function, role function, and overall health status in the European Organization for Research and Treatment of Cancer Core Scale C30 were significantly higher than before treatment (all P<0.05), and the increase was more significant in the observation group (all P<0.05). The median progression free survival and median overall survival in the observation group were 5.9 months and 13.1 months, respectively, significantly longer than those in the control group (4.5 months and 9.6 months) (all P<0.05). During the treatment period, both groups experienced varying degrees of adverse reactions such as hypertension, leukopenia, thrombocytopenia, and liver and kidney damage, but both were mainly grade Ⅰ-Ⅱ. The overall adverse reactions were clinically controllable and tolerable by patients. The incidence of hypertension, thrombocytopenia, hand foot syndrome, and oral ulcers in the observation group was significantly higher than that in the control group (all P<0.05). Conclusions:The combination of apatinib and tirezizumab can effectively regulate the levels of peripheral blood tumor markers and angiogenic regulatory factors in advanced gastric cancer patients who have failed first-line chemotherapy, improve short-term anti-tumor efficacy, and bring more survival benefits to patients.

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.
Humans ; Signal Transduction ; Interferon Type I/metabolism* ; Ossification of Posterior Longitudinal Ligament/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Osteogenesis/genetics* ; Receptor, Interferon alpha-beta/metabolism* ; Male ; Female ; Cell Differentiation ; Middle Aged

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

Parkinsonism is a clinical syndrome caused by many reasons, mainly manifested as bradykinesia, stiffness, static tremor and postural instability. Common disease development patterns include occult onset, gradual development, and little natural remission. However, clinically there are some Parkinsonism that will improve, naturally alleviate or "cure", called reversible parkinsonism (RP). By searching the relevant literature, RP was classified into 12 different types: drugs induced, poisoning induced, infection induced, intracranial vascular induced, structural encephalopathy related, changes in intracranial pressure related, imbalance of internal environment induced, visceral diseases related, alcohol withdrawal related, surgery related, immunization and radiotherapy induced RP. This article aims to provide clinicians with more ideas for the clinical diagnosis and treatment of parkinsonism, so as to promote clinicians to make reasonable identification and diagnosis and treatment of parkinsonism as soon as possible.

Hanger reflex is a common phenomenon in the population that involuntary head and neck rotation or skew occurs when applying pressure to the forehead, tempus or occipitalia with an ordinary wire hanger tightly around the head. The hanger reflex is consistent with the characteristics of sensory tricks in dystonia, and the phenomenon induced by it in normal people should be regarded as negative sensory tricks in dystonia. The mechanism of dystonia behind the hanger reflex and its therapeutic potential deserve more clinicians′ attention.

Objective: To examine the relationship between interpregnancy interval (IPI) and neurodevelopment among 6-month-old infants, so as to provide insights into the prevention of neurodevelopmental abnormalities among infants. Methods: Puerparas with full-term delivery at Anhui Province Maternity and Child Health Hospital from April 2017 to July 2018 and their babies were recruited. The demographic features, behaviors during pregnancy, IPI and birth outcomes were collected through questionnaires and medical records. The neurodevelopment was evaluated using the Ages and Stages Questionnaire (third edition) among infants at 6 months of age. The association between IPI and neurodevelopment was examined using multivariable logistic regression analysis. Results : Totally 485 maternal-newborn pairs were investigated, and the puerparas had a mean age of ( 29.43±4.40 ) years. There were 330 puerparas ( 68.04% ) with normal pre-pregnancy body mass index, 325 puerparas ( 67.01% ) with eutocia, 233 puerparas (48.04%) with the first delivery, 44 puerparas ( 9.07% ) with IPI of less than one year and 208 puerparas ( 42.89% ) with IPI of one year and greater. There were 246 male babies ( 50.72% ) and 437 babies ( 90.10% ) with normal birth weight. A total of 148 newborns were diagnosed with neurodevelopmental abnormalities, with a detection rate of 30.52%. Of all newborns with neurodevelopmental abnormalities, there were 45 babies with communication abnormalities ( 9.28% ), 87 babies with gross motor abnormalities ( 17.94% ), 73 babies with fine motor abnormalities ( 15.05% ), 68 babies with abnormalities of solving problems ( 14.02% ) and 60 babies with personal-social abnormalities ( 12.37% ). Multivariable logistic regression analysis showed a reduced risk of infant's communication abnormalities ( OR=0.273, 95%CI: 0.090-0.833 ), gross motor abnormalities ( OR=0.340, 95%CI: 0.150-0.770 ), fine motor abnormalities ( OR=0.266, 95%CI: 0.106-0.670 ), personal-social abnormalities ( OR=0.321, 95%CI: 0.121-0.851 ) and neurodevelopmental abnormalities ( OR=0.353, 95%CI: 0.171-0.730 ) among puerparas with IPI of one year and greater as compared to those with IPI of less than one year, and no significant difference was seen in infant's neurodevelopmental abnormalities between puerparas with the first delivery and with IPI of less than one year. Conclusion IPI is associated with neurodevelopmental abnormalities among 6-month-old infants.

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

Objective:To evaluate the improvement of papilledema and visual acuities in patients with idiopathic intracranial hypertension (IIH) after venous sinus stenting.Methods:The clinical data of 8 IIH patients who met the inclusion criteria underwent venous sinus stenting between January 2013 and December 2016 at Department of Neurosurgery, Tianjin Huanhu Hospital were analyzed retrospectively. There were 6 females and 3 males,aged (32.9±14.4)years (range:19 to 57 years).The thickness of the retinal nerve fiber layer (RNFL) was measured by optical coherence tomography. Fundus,visual acuity and visual field examination were performed before and after operation. If pressure gradient ≥10 mmHg(1 mmHg=0.133 kPa) across the venous stenosis was indicated by intraoperative pressure measurement,the patient would be treated with venous sinus stenting. Intracranial pressure was measured by lumbar puncture 3 to 7 days after operation. RNFL thickness and eye examination were detected 6 months after surgery. CT venogram was used to observe the sinus venous conditions. Paired t test was used to compare the data before and after surgery. Results:All the 8 patients underwent venous sinus stenting successfully. The mean pressure gradient across the venous stenosis was reduced from (24±9.2) mmHg to (2.6±2.0) mmHg ( t=8.02, P<0.01). Intracranial pressure decreased from preoperative (41.4±12.7) cmH 2O(1 cmH 2O=0.098 kPa) to postoperative (12.9±3.3) cmH 2O ( t=7.08, P<0.01). The RNFL thickness decreased from (275.3±68.3)μm to (131.4±31.8)μm( t=5.80, P<0.05) 6 months after surgery and the baseline visual acuity was improved from( M( Q R))0.24 (0.25) to 0.65 (0.23)( Z=-2.52, P<0.05).Papilledema was significantly improved in 6 patients,and no significant change in 2 patients. CT venogram indicated adjacent stent restenosis in 1 patient. Conclusion:Venous sinus stenting can effectively improve papilledema and visual acuity caused by IIH.