Clinico-pathological and gene features of 15 nemaline myopathy patients from a single Chinese neuromuscular center.

BACKGROUND: Nemaline myopathy, the most common of the congenital myopathies, is caused by various genetic mutations. In this study, we attempted to investigate the clinical features, muscle pathology and genetic features of 15 patients with nemaline myopathy. RESULTS: Among the 15 patients, there were 9 (60.00%) males and 6 (40.00%) females, and 9 (60.00%) of them came from three families respectively. The age of seeing a doctor ranged from 9 to 52 years old, the age of onset was from 5 to 23 years old, and the duration of disease ranged from 3 to 35 years. Ten out of the 15 patients had high arched palate and elongated face. Only one patient had mild respiratory muscle involvement and none had dysphagia. Muscle biopsies were performed in 9 out of the 15 patients. Pathologically, muscle fibers of different sizes, atrophic muscle fibers and compensatory hypertrophic fibers could be found, and occasionally degenerated and necrotic muscle fibers were observed. Different degrees of nemaline bodies aggregation could be seen in all 9 patients. The distribution of type I and type II muscle fibers were significantly abnormal in patients with nemaline myopathy caused by NEB gene, however, it was basically normal in patients with nemaline myopathy caused by TPM3 gene and ACTA1 gene. Electron microscopic analysis of 6 patients showed that nemaline bodies aggregated between myofibrils were found in 5(83.33%) cases, and most of them were located near the Z band, but no intranuclear rods were found. The gene analysis of 15 NM patients showed that three NM-related genes were harbored, including 11 (73.33%) patients with NEB, 3 (20.00%) patients with TPM3, and 1 (6.67%) patient with ACTA1, respectively. A total of 12 mutation sites were identified and included 10 (83.33%) mutations in exon and 2(16.67%) mutations in intron. CONCLUSIONS: The clinical phenotype of nemaline myopathy is highly heterogeneous. Muscle pathology shows that nemaline bodies aggregation is an important feature for the diagnosis of NM. NEB is the most frequent causative gene in this cohort. The splicing mutation, c.21522 + 3A > G may be the hotspot mutation of the NEB gene in Chinese NM patients.

Comparison of clinical outcomes in patients with 4b acute myocardial infarction caused by early and late stent thrombosis / 天津医药

Objective To observe and compare in-hospital and 1-year survival and prognosis of patients with 4b acute myocardial infarction(AMI)caused by early and late stent thrombosis(ST).Methods A total of 302 patients with 4b acute myocardial infarction caused by ST were enrolled in this study from January 2015 to February 2018.ST patients were confirmed by coronary angiography.These patients were divided into two groups:the early ST group(n=26)and the late ST group(n=276)according to the time of ST occurrence.Endpoint events during hospitalization and one year of follow up were compared between the two groups of patients.The primary endpoint events included cardiac death and recurrent AMI.The secondary endpoint events included target lesion revascularization(TLR),re-stent thrombosis,heart failure and stroke.The incidence of no endpoint events was compared between two groups of patients by Kaplan and Meier survival analysis.Cox regression analysis was used to analyze risk factors for endpoint events in patients with type 4b AMI.Results There was no significant difference in the incidence of the primary endpoint events during hospitalization between the two groups(7.7%vs.3.3%,P=0.243).The incidence of heart failure was higher in the early ST group than that of the late ST group(11.5%vs.1.4%,P=0.016).There was no significant difference in the incidence rates of other secondary endpoint events between the two groups(P＞0.05).After a mean follow-up of 1 year,the incidence rates of primary endpoint events and the secondary eendpoint events were higher in the early ST group(20.0%vs.5.9%,P＜0.05 and 36.0%vs.11.5%,P＜0.01)than that of the late ST group.Kaplan and Meier survival analysis showed that the 1-year cumulative incidences of non-primary(P= 0.022)and non-secondary events(P＜0.001)were lower in the early ST group than those of the late ST group.Cox regression analysis showed that hypertension and history of coronary artery bypass grafting were independent risk factors for primary endpoint events in patients with 4b AMI,and intraoperative implantation of intraaortic balloon pump(IABP)and shortening the time from stent thrombosis to balloon dilation(ST to B)were independent protective factor.Conclusion Early ST patients have similar in-hospital outcomes and poor long-term prognosis compared with late ST induced 4b type AMI patients.Intraoperative implantation of IABP and shortening of ST to B time may improve the prognosis of 4b type AMI patients.

Finite element analysis of the effect of bone on occlusal adjustment of right upper first molar implants / 中国组织工程研究

BACKGROUND:Bone tissue remodeling is closely related to stress loading.Currently,there are few studies or guidelines on the relationship between bone and occlusal adjustment of implant prostheses and there is also a lack of scientific evidence. OBJECTIVE:To investigate the effects of different implant occlusal gaps on stress distribution,stress peak and displacement at the implant-bone interface under Ⅰ-Ⅳ bone conditions by a finite element method. METHODS:After scanning the equal-scale tooth model with an optical scanner,equal-scale models of the upper right first molar Straumann 4.8×8 mm BL RC implant and its related components was constructed using Solidworks 2022.Then,using Mimics,Geomagic,and Solidworks software,the maxillary and mandibular bone models of class Ⅰ-Ⅳ bones were established based on the bone classification proposed by ZARB and LEKHOLM in the literature,and the NORTON and TRISI bone density classification method.The models were assembled with the occlusal gaps of 0,20,40,60,80,and 100 μm for the restorations,and an additional set of homogeneous models without density ratio settings was constructed for comparison.After the above models were imported into Hypermesh for meshing,the material assignment,boundary constraints and parameter setting were performed for the finite element analysis.Finally,250 N was used as the loading force to simulate the maxillary and mandibular stress conditions.Stress distribution,peak stress and displacement of the implant-bone interface in each group of models were analyzed and compared. RESULTS AND CONCLUSION:Under the same loading conditions,the stresses in the implant restorations were evenly distributed with the occlusal contact points.When the occlusal gap reached 80 and 100 μm,stress interruptions occurred in the implant crowns under class Ⅰ bone and class Ⅱ,Ⅲ and Ⅳ bones,respectively.The displacement of the implant-bone interface was mainly concentrated in the cortical bone region around the implant and transmitted down the long axis of the implant to the cancellous bone region at the bottom.With the changes of class Ⅰ-Ⅳ jaw bones,the displacement and Von Mises stress in the cortical bone region increased in all groups,and were greater than those in the cancellous bone region.The Von Mises stress in the cancellous bone region was similar to that in the cortical bone region except that it showed a downward trend from class Ⅱ bone.However,when the occlusal gap increased,the stress and displacement peak values in the cortical bone and the cancellous bone showed a decreasing trend.The stress of the implant-bone interface was between 20 MPa and 60 MPa when the occlusal gap was 0-40 μm for class Ⅱ-Ⅳ bones and 60 μm for class Ⅳ bone,and the stress of the other groups was less than 20 MPa.The Von Mises stress was mainly concentrated in the neck of the implant,and the peak value of von Mises stress in class Ⅱ-Ⅳ bones with the occlusal gap of 20 μm was higher than that(144.10 MPa)in class Ⅰ bone with the occlusal gap of 0 μm.In the homogeneous model with different elastic moduli,the distribution of stress and displacement was more uniform than that in the heterogeneous model and the occlusal space should increase with the decrease of jaw bone density in clinical practice.To conclude,from the perspective of biomechanics,the alveolar bone should be taken into account in the occlusal adjustment of implant denture.An occlusal gap of 20-40 μm between a single dental implant and a natural tooth in the opposite jaw is a relatively suitable solution for occlusal adjustment under different bone conditions.However,due to the particularity of finite element analysis method,it needs to be further studied in combination with clinical practice.

Research on the current status,hotspots,and evolution trends of integrity construction in public hospi-tals:a citespace visualization analysis / 现代医院

Objective To explore the research status,hot topics and trends in the construction of integrity in public hos-pitals in China,provide references for the research on integrity construction in public hospitals and promote their high-quality de-velopment.Methods The relevant literature on the construction of integrity in public hospitals from 2009 to 2022 was collected from the China National Knowledge Infrastructure(CNKI)database.CiteSpace software was used to analyze the selected litera-ture in terms of publication timeline,author co-citation,institution co-citation,keyword co-occurrence,keyword clustering and keyword burst analysis,and visualize the knowledge graph.Results The research on the construction of integrity in public hos-pitals in China showed an upward trend from 2009 to 2022.The hot topics in the research mainly focused on incorruptible medical practices,integrity risks and integrity culture.The keyword burst analysis revealed that discipline inspection and supervision,in-formation platforms and institutional development were the future research directions.Conclusion The research on the construc-tion of integrity in public hospitals in China has a clear policy orientation,and various subfields are being explored.Internal inde-pendent research is predominant,while collaboration among multiple scholars and institutions needs to be strengthened.The con-struction of integrity in public hospitals in China mainly focuses on three areas.

Efficacy and safety of ruxolitinib for refractory graft-versus-host disease in Chinese population: a Meta-analysis / 白血病·淋巴瘤

Objective:To systematically evaluate the efficacy and safety of ruxolitinib in the treatment of Chinese patients with refractory graft-versus-host disease(SR-GVHD) by using meta-analysis.Methods:China National Knowledge Infrastructure(CNKI), WanFang database, VIP database, China Biology Medicine disc, PubMed, Ebscore Medline, EMBASE, Web of Science Core Collection and Cochrane Library were searched by using "ruxolitinib" "Graft vs Host Disease" "graft versus host disease" "Graft-Versus-Host Disease" as key words. The retrieve time was from the establishment of the database to December 7th, 2021. The related literatures of ruxolitinib for Chinese patients with SR-GVHD were screened according to inclusion and exclusion criteria, and the characteristics of the literatures were extracted. Outcomes indexes included overall objective response rate (ORR), proportion of hormone reduction and discontinuation, survival indexes and incidence of adverse events. Meta-analysis of ORR, remission rate of affected organs, 12-month overall survival rate, overall mortality and mortality due to graft-versus-host disease (GVHD) were performed by using Stata 16.0 software or R3.6.3 software. The statistics analysis was performed on the hormone usage and adverse events.Results:A total of 19 literatures involving 775 Chinese patients with SR-GVHD treated by ruxolitinib were included. Meta analysis showed that the ORR of ruxolitinib for treatment of acute GVHD (aGVHD) was 84% (285/339), with moderate heterogeneity among studies ( I2 = 62.04%, P<0.01), and the complete remission (CR) rate, partial remission (PR) rate and non-remission (NR) rate was 56% (190/339), 28% (95/339), and 14%(47/339), respectively. The ORR of ruxolitinib for treatment of chronic GVHD (cGVHD) was 77% (332/431), with moderate heterogeneity among studies ( I2 = 50.17%, P = 0.02), and the CR rate, PR rate and NR rate was 36% (155/431), 41% (177/431) and 21% (91/431), respectively. As for hormone usage, 46.51% of aGVHD patients had steroid reduction and 34.88% patients had steroid discontinuation. Similarly, 28.2% of patients with cGVHD had steroid reduction and 36.9% had steroid discontinuation. The overall 12-month survival rate of patients with SR-GVHD after the treatment of ruxolitinib was 71% (95% CI: 63%-79%, I2 = 72.70%, P<0.01). Adverse events occurred for 760 times in total, among which 287 times (36.0%) of viral infection and 269 times (34.7%) of hemocytopenia were the most common adverse events. Conclusions:Ruxolitinib is effective in the treatment of Chinese patients with SR-GVHD, and it helps reduce hormone-dependency and prolong the survival time.

Vector analysis of toric implantable collamer lens V4c implantation in correcting moderate to high myopia with high astigmatism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical effect of toric implantable collamer lens(TICL)V4c for correcting moderate to high myopia with high astigmatism using vector analysis and quality of life impact of refractive correction(QIRC).METHODS: Retrospective case series. A total of 55 patients(90 eyes)with moderate to high myopia and high astigmatism who received TICL V4c implantation in the refraction surgery center of ophthalmology department in our hospital from January 2019 to December 2022 were collected. Followed-up for 1 a, the uncorrected distance visual acuity(UDVA), best corrected visual acuity(BCVA)and diopters were observed. Alpins vector analysis was used to evaluate the effect of astigmatism correction, and QIRC scale was used to evaluate patients' quality of life.RESULTS: At 1 a postoperatively, the UDVA of 98% eyes was the same or better than pre-operative BCVA, the safety index was 1.11±0.14, and the efficacy index was 1.11±0.15. The angle of error of 97% of the astigmatic eyes was within ±15°. The results of vector analysis showed that correction index was 0.83±0.13, angle of error was 1.00±4.49°, and index of success was 0.21±0.15. The total higher order aberrations under a pupil diameter of 6 mm was significantly increased compared with preoperatively(P&#x003C;0.05), the QIRC score was significantly better than that before surgery(P&#x003C;0.001), and the increase of total QIRC scores was positively correlated with preoperative spherical equivalent(rs=0.215, P&#x003C;0.05), indicating that the higher degree of myopia before surgery the patients, the better the quality of life after TICL implantation.CONCLUSION: TICL V4c implantation for the correction of moderate to high myopia with high astigmatism is safe and effective, and the patients' quality of life significantly improved after surgery.

Neuroimaging research status of persistent postural-perceptual dizziness / 中风与神经疾病杂志

@#Persistent postural-perceptual dizziness （PPPD） is a common clinical chronic dizziness disease，with persistent dizziness，instability，or non-rotational vertigo as the main symptom. It may be aggravated by postural changes，active/passive movements，and exposure to complex visual environments. At present，it is believed that the occurrence of PPPD may be related to the failure of postural control readaptation and abnormal cortical multisensory integration，but the specific pathophysiological mechanism is not clear. In recent years，with the continuous application of neuroimaging technology in the field of vertigo diseases，it has been found that in patients with PPPD，the brain structure，function，and connectivity related to vestibular multisensory and spatial orientation are decreased，while the function and connectivity related to visual processing are enhanced. At the same time，various psychiatric factors （such as anxiety，depression，and neuroticism） as well as triggers may be involved in regulating the brain structure of people with PPPD，which helps explain the differences in outcomes between studies. The above neuroimaging findings are helpful for the early diagnosis and treatment of PPPD. Therefore，this paper reviews the neuroimaging studies of PPPD to provide a reference for explaining the pathophysiological mechanism of PPPD.

Analysis of revascularization strategies for elderly patients with ST-segment elevation myocardial infarction and multivessel disease / 中华老年医学杂志

Objective:To compare the effects of staged percutaneous coronary intervention(PCI)after emergency PCI and emergency culprit-only PCI on clinical outcomes of elderly patients with ST-segment elevation myocardial infarction(STEMI)and multivessel disease.Methods:A retrospective analysis was performed on 389 elderly patients with STEMI and multivessel lesions, aged ≥70 years and within 12 h of onset, admitted to the Clinical College of Thoracic Medicine, Tianjin Medical University, between January 2014 and September 2019.According to different revascularization strategies, enrolled patients were divided into the culprit-only PCI group(79.18%, 308)and the staged PCI group(20.82%, 81). Kaplan-Meier analysis and the Cox proportional hazards regression model were used to compare the incidences of major adverse cardiac and cerebrovascular events(MACCE), all-cause death, cardiac death, recurrent myocardial infarction, stroke and ischemia-driven revascularization between the two groups and to evaluate the effects of different revascularization strategies on MACCE and all-cause death.Then subgroup analysis was performed.Results:During a 56-month follow-up, 131 patients developed MACCE and 96 patients died.Compared with the culprit-only PCI group, the staged PCI group had a lower risk of MACCE( HR: 0.404, 95% CI: 0.227-0.716, P=0.002), all-cause death( HR: 0.354, 95% CI: 0.171-0.730, P=0.005), cardiac death( HR: 0.363, 95% CI: 0.157-0.838, P=0.018), and recurrent myocardial infarction( HR: 0.229, 95% CI: 0.055-0.953, P=0.043). There was no significant difference in the incidence of stroke or ischemia-driven revascularization between the two groups( P>0.05). The reduced risk with staged PCI for MACCE and for all-cause mortality persisted in all subgroups.Multivariate Cox proportional hazards regression revealed that, after adjusting for confounding factors, staged PCI was an independent protective factor for MACCE( HR: 0.44, 95% CI: 0.239-0.815, P=0.009)and for all-cause death( HR: 0.390, 95% CI: 0.90, P=0.020). Conclusion:Compared with culprit-only PCI, staged PCI can significantly improve the long-term prognosis of elderly patients ≥70 years with STEMI and multivessel disease within 12 h of onset.

Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

Nuclear factor-Y mediates pancreatic β-cell compensation by repressing reactive oxygen species-induced apoptosis under metabolic stress / 中华医学杂志(英文版)

BACKGROUND@#Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear.@*METHODS@#In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress.@*RESULTS@#Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment.@*CONCLUSION@#Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.

[Retracted] MicroRNA-199b targets the regulation of ZEB1 expression to inhibit cell proliferation, migration and invasion in non­small cell lung cancer.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that cell migration assay data shown in Figs. 2D and 4D were strikingly similar to data that had appeared in different form in other articles by different authors (in addition to the apparent duplication of some of these data within this paper itself). Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 5007­5014, 2017; DOI: 10.3892/mmr.2017.7195].

Long-term development of dynamic changes in neurovascular coupling after acute temporal lobe epilepsy.

Epilepsy is an abnormal brain state that may be induced by synchronous neuronal activation and also abnormalities in energy metabolism or the oxygen supply vascular system. Neurovascular coupling (NVC), the relationship between neuron, capillary, and penetrating artery, remains unexplored on a fine-scale with respect to the pathology process after acute temporal lobe epilepsy (TLE). Here we use two-photon microscopy (TPM) to provide high temporal-spatial resolution imaging to identify changes in NVC during spontaneous and electro-stimulated (ES) states in awake mice. Implantation of a long-term craniotomy window allowed TPM recording of the pathological development after the acute Kainic Acid temporal lobe epilepsy model. Our results provide direct evidence that the capillary and penetrating artery are not correlated to rhythmic neuronal activity during acute epilepsy. During the CSD period, NVC shows a strong correlation. We demonstrate that NVC exhibits nonlinear dynamics after status epilepticus. Furthermore, the vascular correlation to neuronal signals in spontaneous and ES states shows dynamic changes which correlate to the evolution after acute TLE. Understanding NVC in all TLE stages, from the acute through the TLE pathological development, may provide new therapeutic pathways.

Carboplatin-induced renal salt-wasting syndrome in pediatric patients with intracranial germ cell tumors and concomitant diabetes insipidus.

We report a case series of 14 children with intracranial germ cell tumor and concomitant central diabetes insipidus, who developed hyponatremia secondary to renal salt-wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum-based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatremia can be asymptomatic until it is severe.

Role of sphingomyelinases in hepatocellular carcinoma / 临床肝胆病杂志

Sphingomyelinases (SMase) are the main enzymes that regulate the signaling pathway of sphingomyelin and the metabolism of related products, and they are involved in the key steps of the complex metabolic process of sphingomyelin. In recent years, many studies have shown that SMase is involved in the biological processes such as cell cycle arrest, cell migration, and inflammation and promotes the development and progression of hepatocellular carcinoma by regulating the apoptosis and proliferation of tumor stem cells. SMase has an important potential biological value in the development, progression, diagnosis, and treatment of hepatocellular carcinoma. This article summarizes the exact role of SMase in the development and progression of hepatocellular carcinoma, in order to provide new ideas and strategies for the clinical treatment of hepatocellular carcinoma and the development of new drugs.

Influence of eye movement on precision of corneal ablation and refraction status in SMILE / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the influence of slight eye movement during laser scanning on femtosecond laser precision of corneal ablation and postoperative refractive status in small incision lenticule extraction(SMILE). METHODS: Totally 32 patients(62 eyes)who underwent SMILE surgery in our hospital from January 2019 to March 2021 were included and divided into the movement group and the fixation group according to whether the eyeballs were slightly moved during the operation, and select patients with slightly moved monocular eyeballs for binocular pairing. The actual difference of absolute value of corneal absolute cutting error(ACE), astigmatism error(AE), absolute refractive error(ARE)and absolute visual error(AVE)was compared between the movement group and the fixation group and the two eyes of the patients with slight ocular movement in one eye at 1mo after surgery, and the surgical images were quantified to analyze the correlation between the amplitude of ocular movement and AE, and to compare the effects of the area, layer and direction of slight eye movement on ACE.RESULTS: There were no differences in all observed results between movement group and fixation group(P&#x003E;0.05). Patients with slight movement of one eye had a difference in binocular AE(0.57±0.31D vs 0.33±0.27D, P&#x003C;0.05), and the amplitude of movement was positively correlated with AE at 1mo after surgery(r=0.564, P&#x003C;0.05). There was no statistical differences in ACE at 1mo after surgery in patients with slight ocular movement in different regions(central/peripheral), layers(upper/lower lens)and direction(nasal/temporal)(all P&#x003E;0.05).CONCLUSION:The slight eye movement during laser scanning in SMILE has no significant influence on precision of corneal ablation. It mainly causes decentered ablation and the changes of corneal astigmatism, which has little effect on the spherical equivalent and visual acuity.

Pharmacoeconomic evaluation of Keluoxin capsule combined with chemical medicine in the treatment of diabetic kidney disease / 中国药房

OBJECTIVE To evaluat e the cost-effectiveness of Keluoxin capsule combi ned with chemical medicine in the treatment of diabetic kidney disease （DKD）from the perspective of the whole society. METHODS Six-state Markov model with 1 year cycle and 40 years time horizon was constructed by means of secondary literature review ，medical record analysis of sample hospital and clinical expert consultation. The cost-effectiveness of Keluoxin capsule combined with chemical medicine versus chemical medicine alone for DKD was evaluated by taking the quality-adjusted life year （QALY）as the output index ，setting the discount rate as 5％，and taking one time domestic gross domestic product （GDP）per capita in 2020 of China as the judgement threshold of incremental cost-effectiveness ratio （ICER）. RESULTS Within 40 years，Keluoxin capsule combined with chemical medicine group spent 8 644.09 yuan per capita more than chemical medicine alone group ，and gained more 0.143 QALYs；ICER was 60 460.25 yuan/QALY，which was less than one times GDP per capita of China in 2020（72 447 yuan）. The results of sensitivity analysis showed that the annual days of using Keluoxin capsule ，the health utility value of DKD at early stage had a great influence on the results of cost-effectiveness analysis. The results of probabilistic sensitivity analysis suggested that the basic analysis results of this study were robust. CONCLUSIONS At the current price level ，Keluoxin capsule combined with chemical medicine is more cost-effective to treat DKD than chemical medicine alone. The dosage of Keluoxin capsule and health utility value should be paid attention in specific decision- bjmu.edu.cn making scenarios.

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells. @*Materials and Methods@#nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro. @*Results@#A high-affinity peptide (nABPD1, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells. @*Conclusion@#nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

[Effects of long-term nitrogen addition on the nitrogen pools in a meadow steppe ecosystem]. / é•¿æœŸæ°®æ·»åŠ å¯¹è‰ç”¸è‰åŽŸç”Ÿæ€ç³»ç»Ÿæ°®åº“çš„å½±å“.

Increasing atmospheric nitrogen (N) deposition greatly affects species diversity, productivity, and stability of ecosystems. It is thus of the great importance to understand how grassland N pools respond to the increased atmospheric N deposition. This study was conducted in a meadow steppe in Erguna, Inner Mongolia, China. There were six levels of N addition (i.e., 0, 2, 5, 10, 20 and 50 g·m-2·a-1) and two levels of mowing (i.e., mowing and unmown). Samples of aboveground tissues of dominant plant, root, aboveground litter, and soil to the depth of 100 cm were collected in the seventh year after treatments. The N content was measured and the N pool was calculated. The results showed that N addition significantly increased the N content of aboveground plant tissues and litter, as well as N pools of Leymus chinensis, plant community, litter and ecosystem. Mowing significantly increased the N content of L. chinensis leaf and litter, but reduced N pools of L. chinensis, plant community and litter, and did not affect their responses to N addition. There was a significant interactive effect between mowing and N addition on plant community N pool. High levels of N addition in the unmown treatment led to more N stored in the litter pool, with the saturation threshold for the plant community N pool occurred at 10 g·m-2·a-1. Under mowing treatment, the plant community N pool increased with the increasing N addition, and more N stored in plant community N pool after mowing. Mowing could alleviate the negative impacts of increasing N deposition on biodiversity and ecosystem stability, and extended postponing the occurrence of ecosystem N saturation induced by increasing N deposition.

Efficacy and safety of endostatin in combination with chemotherapy in small cell lung cancer: a phase 2 single-arm multicenter open-label trial.

BACKGROUND: Small-cell lung cancer (SCLC) is a type of lung cancer with high invasiveness and poor prognosis. Although SCLC is effective for initial treatment, the vast majority of patients will relapse, the efficacy of posterior line therapy is limited, and there is a lack of effective treatment. At the same time, in the past 30 years, there has been little progress in first-line treatment. With the progress of antiangiogenic therapy, whether it can be used in the treatment of SCLC is worth exploring. Therefore, a single-arm multicenter clinical study was conducted on the efficacy, optimization, and safety of endostatin combined chemotherapy in SCLC. METHODS: This study is a prospective non-blind single-arm multicenter study. From January 2016 to July 2019, a total of 22 patients with histologically diagnosed SCLC were enrolled in three centers. The treatment regimen was as follows: continuous intravenous pump infusion of endostatin (90 mg) for 72 hours, 3 days before chemotherapy, and continuous pump infusion of endostatin (120 mg) for 96 hours the next day following the infusion of chemotherapeutic drugs; the chemotherapy regimen was administered with standard platinum combined with etoposide once every 21 days. After six cycles, endostatin maintenance therapy was used until the disease progressed or intolerable adverse reactions occurred. The therapeutic effect was evaluated by imaging and oncology markers every two cycles, and the adverse reactions, tumor progression time, and patient survival time were recorded. RESULTS: Among the 21 patients analyzed, the median progression-free survival (PFS) was 8.0 months, the median overall survival (OS) was 13.6 months, the objective effective rate (ORR) was 61.9%, and the disease control rate (DCR) was 95.2%. All patients tolerated the treatment. The main adverse reactions were myelosuppression, albuminuria, nausea, and vomiting. The incidence of grade 3 or 4 adverse reactions was 7.2%, which could be relieved by symptomatic support treatment. There were no treatment-related deaths. CONCLUSIONS: Endostatin combined with platinum-etoposide is safe and effective in the treatment of SCLC.

Clinical characteristics of Guillain-Barré syndrome combined with hyponatremia in Southern China and its risk factors for prognosis: a multi-center retrospective analysis / 中华神经医学杂志

Objective:To investigate the clinical characteristics of Guillain-Barré syndrome (GBS) combined with hyponatremia in Southern China and its risk factors for prognosis.Methods:The retrospective cohort study involved patients who met the diagnostic criteria of GBS from 18 upper first-class hospitals of 6 provinces/cities in southern China (south of Huaihe River) from January 1, 2013 to September 30, 2016. The clinical data of these patients were collected. According to serum sodium levels, they were divided into hyponatremia group (serum sodium concentration<135 mmol/L) and normal serum sodium group (serum sodium concentrations≥135 mmol/L). Based on Medical Research Coucil sum scores at nadir, these patients were divided into mild GBS group (>40), moderate GBS group (30-40), and severe GBS group (<30). Furthermore, according to the Hughes GBS disability scale (H-GBS-DS) scores at discharge, these GBS patients with hyponatremia were divided into favorable prognosis group (H-GBS-DS<3) and poor prognosis group (H-GBS-DS≥3). The incidence of hyponatremia in patients from the mild GBS group, moderate GBS group, and severe GBS group were compared. Multivariate Logistic regression analysis was performed to determine the clinical risk factors for hyponatremia in GBS patients. The clinical data of hyponatremia patients from favorable prognosis group and poor prognosis group were compared; multivariate Logistic regression analysis was used to determine the risk factors for poor prognosis in GBS patients with hyponatremia.Results:(1) Among the 570 patients, 354 had mild GBS, 94 had moderate GBS, and 122 had severe GBS; 134 GBS patients were combined with hyponatremia, 436 GBS patients had normal serum sodium. The hyponatremia incidence in mild, moderate and severe GBS groups increased successively, ( P<0.05). Multivariate Logistic regression analysis showed that facial paralysis ( OR=1.979, 95%CI: 1.172-3.342, P=0.011), respiratory muscle paralysis ( OR=3.218, 95%CI: 1.611-6.428, P=0.001), secondary pulmonary infection ( OR=4.822, 95%CI: 2.835-8.201, P=0.000), severe GBS ( OR=2.611, 95%CI: 1.444-4.721, P=0.001) and length of hospital stay ( OR=1.029, 95%CI: 1.009-1.050, P=0.004) were risk factors for hyponatremia in GBS patients. (2) Among 134 GBS patients with hyponatremia, 80 had poor prognosis and 54 had favorable prognosis. As compared with the favorable group, the poor prognosis group had significantly lower proportion of patients with extraocular muscle paralysis, statistically higher proportions of patients with respiratory muscle paralysis and secondary pulmonary infection, significantly different severities of GBS, signficantly higher proportion of patients accepted intravenous immunoglobulin (IVIG) and hormone treatments, statistically longer length of hospital stay ( P<0.05). Respiratory muscle paralysis ( OR=25.590, 95%CI: 9.433-69.423, P=0.000), moderate GBS ( OR=17.030, 95%CI: 8.441-34.361, P=0.000), and severe GBS ( OR=51.042, 95%CI: 24.596-105.926, P=0.000) were independent risk factors for poor short-term prognosis of GBS patients with hyponatremia. Conclusions:Severe GBS patients with facial paralysis, respiratory muscle palsy, secondary pulmonary infection, and long hospital stay trend to have hyponatremia. Hyponatremia patients with respiratory muscle paralysis and moderate/severe GBS have poor short-term prognosis.