A morphological study of the foveal avascular zone in patients with diabetes mellitus using optical coherence tomography angiography.

PURPOSE: To investigate the area and radius of the foveal avascular zone (FAZ) in patients with diabetes mellitus (DM) using optical coherence tomography (OCT) angiography. METHODS: Sixty-five patients with DM (113 eyes) and 62 healthy controls (85 eyes) were included in the study. All of the participants underwent examination with OCT angiography. The vertical radius (VR), horizontal radius (HR) and area of the FAZ were measured. RESULTS: The differences in HR, VR and area between the control and DM groups were statistically significant (p = 0.01, 0.00 and 0.00, respectively). There were no statistically significant differences between the control group and the no-diabetic retinopathy (DR) group in HR or VR (p = 0.07 and 0.08, respectively), but there was a statistically significant difference in area (p = 0.04). The size of the FAZ was greater in patients with DR compared to the control group. The differences in HR, VR and area were statistically significant (p = 0.01, 0.00 and 0.00, respectively). In addition, the clinically significant macular oedema (CSME) group also had a larger FAZ area than the non-CSME group (p = 0.02). CONCLUSIONS: Patients with DM had a larger FAZ, and patients with more severely damaged retinas had a much larger FAZ. OCT angiography is a new convenient and noninvasive method for studying the FAZ. This novel examination will yield considerable amounts of data that cannot be obtained using previous research methods.

Effects of proprioceptive training on gait and plantar pressure after anterior cruciate ligament reconstruction: study protocol for a randomized controlled trial.

BACKGROUND: People who have undergone anterior cruciate ligament reconstruction have an increased risk of osteoarthritis. Abnormality of lower limb kinematics will occur after the operation. This may be related to lower limb muscle strength, the co-excitation of hamstrings and quadriceps femoris, and the weakness of proprioception. Proprioceptive training can improve the proprioception of lower limbs and promote the recovery of lower limb kinematics. Our research objective is to observe whether proprioceptive training can improve the proprioception of lower limbs within 3 months after surgery and whether the recovery of proprioception can correct the abnormal lower limb kinematics. The secondary objective is to explore the underlying mechanism of postoperative lower limb gait abnormalities. METHODS/DESIGN: This study is a prospective single-center randomized clinical trial to be conducted in the Sports Medicine and Orthopedics of Zhongda Hospital Southeast University. Forty participants aged 18-50, preparing to undergo anterior cruciate ligament reconstruction, and initial anterior cruciate ligament reconstruction using hamstring tendons as grafts will be randomly assigned to the intervention or comparator group. People in the intervention group will add proprioceptive training three times a week, 20 min each time. The intervention will be conducted on the first day after surgery. The researcher mainly collects the data of joint of sense, gait, and plantar pressure. The assessment will be divided into three stages: after signing the informed consent form (within 2 weeks before surgery), 6 weeks after surgery, and 12 weeks after surgery. DISCUSSION: The main purpose of our study is to explore whether the proprioception of patients after anterior cruciate ligament reconstruction is weakened, whether the lower limb kinematics is abnormal and whether the lower limb kinematics can be corrected through proprioceptive training. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200065808. Registered on 15 November 2022; Version 1.

External validation of a deep learning detection system for glaucomatous optic neuropathy: a real-world multicentre study.

OBJECTIVES: To conduct an external validation of an automated artificial intelligence (AI) diagnostic system using fundus photographs from a real-life multicentre cohort. METHODS: We designed external validation in multiple scenarios, consisting of 3049 images from Qilu Hospital of Shandong University in China (QHSDU, validation dataset 1), 7495 images from three other hospitals in China (validation dataset 2), and 516 images from high myopia (HM) population of QHSDU (validation dataset 3). The corresponding sensitivity, specificity and accuracy of this AI diagnostic system to identify glaucomatous optic neuropathy (GON) were calculated. RESULTS: In validation datasets 1 and 2, the algorithm yielded accuracy of 93.18% and 91.40%, area under the receiver operating curves (AUC) of 95.17% and 96.64%, and significantly higher sensitivity of 91.75% and 91.41%, respectively, compared to manual graders. On the subsets complicated with retinal comorbidities, such as diabetic retinopathy or age-related macular degeneration, in validation datasets 1 and 2, the algorithm achieved accuracy of 87.54% and 93.81%, and AUC of 97.02% and 97.46%, respectively. In validation dataset 3, the algorithm achieved comparable accuracy of 81.98% and AUC of 87.49%, with a sensitivity of 83.61% and specificity of 81.76% on GON recognition specifically in the HM population. CONCLUSIONS: With acceptable generalization capability across varying levels of image quality, different clinical centres, or certain retinal comorbidities, such as HM, the automatic AI diagnostic system had the potential to provide expert-level glaucoma detection.

Effects of different water quality regulators on growth performance, immunologic function, and domestic water quality of GIFT tilapia.

Water quality regulation is widely recognized as a highly effective strategy for disease prevention in the field of aquaculture, and it holds significant potential for the development of sustainable aquaculture. Herein, four water quality regulators, including potassium monopersulfate (KMPS), tetrakis hydroxymethyl phosphonium sulfate (THPS), bacillus subtilis (BS), and chitosan (CS), were added to the culture water of Oreochromis niloticus (GIFT tilapia) every seven days. Subsequently, the effects of these four water quality regulators on GIFT tilapia were comprehensively evaluated by measuring the water quality index of daily growth-related performance and immune indexes of GIFT tilapia. The findings indicated that implementing the four water quality regulators resulted in a decrease in the content of ammonia nitrogen, active phosphate, nitrite, total organic carbon (TOC), and chemical oxygen demand (COD) in the water. Additionally, these regulators were found to maintain dissolved oxygen (DO) levels and pH of the water effectively. Furthermore, using these regulators demonstrated positive effects on various physiological parameters of GIFT tilapia, including improvements in final body weight, weight gain rate (WGR), specific growth rate (SGR), condition factor (CF), feed conversion ratio (FCR), spleen index (SI), hepato-somatic index (HSI), immune cell count, the activity of antioxidant-related enzymes (Nitric oxide, NO and Superoxide dismutase, SOD), and mRNA expression levels of immunity-related factors (Tumor Necrosis Factor-alpha, TNF-α and Interleukin-1 beta, IL-1ß) in the liver and spleen. Notably, the most significant improvements were observed in the groups treated with the BS and CS water quality regulators. Moreover, BS and CS groups exhibited significantly higher serum levels of albumin (ALB) and total protein (TP) (P < 0.05), whereas the other indicators showed no significant difference (P > 0.05) compared to the control group. However, the KMPS and THPS groups of GIFT tilapia exhibited significantly higher serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE) and blood urea nitrogen (BUN) (P < 0.05), whereas they exhibited significantly decreased HSI (P < 0.05). In addition, the partially pathological observations revealed the presence of cell vacuolation, nuclear shrinkage, and pyknosis within the liver. In conclusion, these four water quality regulators, mainly BS and CS, could improve the growth performance and immunity of GIFT tilapia to varying degrees by regulating the water quality and then further increasing the expression levels of immune-related factors or the activity of antioxidant-related enzymes of GIFT tilapia. On the contrary, the prolonged use of KMPS and THPS may gradually diminish their growth-enhancing properties and potentially hinder the growth of GIFT tilapia.

Association Between Retinal Microvascular Metrics Using Optical Coherence Tomography Angiography and Carotid Artery Stenosis in a Chinese Cohort.

Objectives: The main aim was to investigate the association between retinal microvascular metrics using optical coherence tomography angiography (OCTA) and carotid artery stenosis (CAS) in an aging Chinese cohort. Methods: In this cross-sectional and observational study, 138 eyes of 138 participants were examined. Indices of the microcirculation measured by OCTA included mean vessel density (VD), skeleton density (SD), vessel diameter index (VDI), fractal dimension (FD) and foveal avascular zone (FAZ) of the superficial retinal layer (SRL) and deep retinal layer (DRL), and peripapillary vessel caliber. The correlation of these indices with the carotid atherosclerotic lesions including carotid intima media thickness (CIMT) and common carotid artery (CCA) plaque was assessed. Results: A total of 72 of 138 eyes demonstrated an increased (≥1 mm) CIMT, and 32 of the eyes presented common carotid plaques. Macular VD, SD, and FD were decreased with the increasing CCA caliber diameter (p < 0.05, respectively). Superficial and deep macular FDs were negatively associated with CIMT as well as the existence of CCA plaques (p < 0.05, respectively). Conclusion: Changes in retinal microvasculature accessed by OCTA may be used as one of the non-invasive early indicators to monitor asymptomatic CAS.

Is the Lesser Khingan Suitable for the Amur Tiger Restoration? Perspectives with the Current State of the Habitat and Prey Base.

The Amur tiger (Panthera tigris) has a status of being endangered on the world's IUCN red list. The northwestern part of its range is situated in Russia and China, where tigers were exterminated by humans in the 1950-1970s. To restore tiger population within a historical range, an estimation of the habitat suitability is firstly needed. The Lesser Khingan mountains (Heilongjiang) was analyzed. Habitat types were mapped by satellite images analysis and field proven. The potential habitats of the main tiger's prey species (wild boar (Sus scrofa), roe deer (Capreolus pygargus), and red deer (Cervus elaphus xanthopygus) were also assessed. Maximum entropy and linear discriminant analysis methods were applied and compared for species distribution modeling (SDM). Species distribution maps were used to design an ecological network. The fragmentation of habitat patches was evaluated by spatial ecological metrics. The habitat patches with the best metrics were assigned as cores for the ecological network, which were connected by calculated corridors. The least cost distance method (based on distance to roads and settlements) was used. The recovery of the Amur tiger in habitats of China's Lesser Khingan is shown to be possible. Types of habitats were calculated as natural corridors for moving tigers. They are mainly located at the forests' edges and characterized with various canopy structures and high variability in the tree species composition. Three potential transboundary corridors are described: (a) foothills and low mountains of the northern Lesser Khingan; (b) connection between the southeast Lesser Khingan and the western part of the Wandashan mountain system; and (c) corridor within foothills and low mountains of the eastern part of Lesser Khingan. It is recommended to establish protected areas for the important tiger core habitats, and the main optimal ways for their migrations are described during the current investigation. Moreover, it is necessary to implement habitat recovery activities for key areas.

The effectiveness of artificial intelligence-based automated grading and training system in education of manual detection of diabetic retinopathy.

Background: The purpose of this study is to develop an artificial intelligence (AI)-based automated diabetic retinopathy (DR) grading and training system from a real-world diabetic dataset of China, and in particular, to investigate its effectiveness as a learning tool of DR manual grading for medical students. Methods: We developed an automated DR grading and training system equipped with an AI-driven diagnosis algorithm to highlight highly prognostic related regions in the input image. Less experienced prospective physicians received pre- and post-training tests by the AI diagnosis platform. Then, changes in the diagnostic accuracy of the participants were evaluated. Results: We randomly selected 8,063 cases diagnosed with DR and 7,925 with non-DR fundus images from type 2 diabetes patients. The automated DR grading system we developed achieved accuracy, sensitivity/specificity, and AUC values of 0.965, 0.965/0.966, and 0.980 for moderate or worse DR (95 percent CI: 0.976-0.984). When the graders received assistance from the output of the AI system, the metrics were enhanced in varying degrees. The automated DR grading system helped to improve the accuracy of human graders, i.e., junior residents and medical students, from 0.947 and 0.915 to 0.978 and 0.954, respectively. Conclusion: The AI-based systemdemonstrated high diagnostic accuracy for the detection of DR on fundus images from real-world diabetics, and could be utilized as a training aid system for trainees lacking formal instruction on DR management.

Worse Sleep Quality Aggravates the Motor and Non-Motor Symptoms in Parkinson's Disease.

Backgrounds: Sleep disorders are the most common and disabling symptoms in patients with Parkinson's disease (PD). Understanding the associations between sleep characteristics and motor and non-motor symptoms (NMSs) in PD can provide evidence to guide therapeutic interventions and nursing strategies. We aimed to investigate the association between sleep characteristics and motor function and NMSs in PD using multiple approaches. Methods: A total of 328 participants were included, and all participants underwent Pittsburgh Sleep Quality Index (PSQI) evaluation and clinical assessments of PD symptoms. We conducted Spearman's correlation to evaluate the associations between sleep and PD symptoms, nonlinear regression to assess the relationships between sleep habits and PD, and mediated analyses to test the effects of NMSs on global PSQI and PD severity, quality of life, and motor symptoms. Results: Poor sleep was associated with more severe PD symptoms. In addition, the reflection point for bedtime was around 21:52, associated with motor symptoms, and insufficient and excessive total time spent in bed and nocturnal sleep duration were correlated with higher NMS burdens. The optimal points were 8-9.2 and 6.2-6.9 h, respectively. It was also discovered that NMSs played the mediating roles in global sleep with the quality of life, PD stages, and motor symptoms to a varying range of 6.8-95.4%. Conclusions: Sleep disorders have a significant effect on the burden of PD symptoms. The current findings provide new insights into the monitoring and management of sleep and PD and need to be further explored in the future studies.

Habitat evaluation of wild Amur tiger (Panthera tigris altaica) and conservation priority setting in north-eastern China.

The Amur Tiger (Panthera tigris altaica) is one of the world's most endangered species. Recently, habitat fragmentation, food scarcity and human hunting have drastically reduced the population size and distribution areas of Amur tigers in the wild, leaving them on the verge of extinction. Presently, they are only found in the north-eastern part of China. In this study, we developed a reference framework using methods and technologies of analytic hierarchy process (AHP), remote sensing (RS), geographic information system (GIS), GAP analysis and Natural Break (Jenks) classification to evaluate the habitat and to set the conservation priorities for Amur tigers in eastern areas of Heilongjiang and Jilin Provinces of northeast China. We proposed a Habitat Suitability Index (HSI) incorporating 7 factors covering natural conditions and human disturbance. Based on the HSI values, the suitability was classified into five levels from the most to not suitable. Finally, according to results of GAP analysis, we identified six conservation priorities and designed a conservation landscape incorporating four new nature reserves, enlarging two existing ones, and creating four linkages for Amur tigers in northeast China. The case study showed that the core habitats (the most suitable and highly suitable habitats) identified for Amur tigers covered 35,547 km(2), accounting for approximately 26.71% of the total study area (1,33,093 km(2)). However, existing nature reserves protected only (7124 km(2) or) 20.04% of the identified core habitats. Thus, enlargement of current reserves is necessary and urgent for the tiger's conservation and restoration. Moreover, the establishment of wildlife corridors linking core habitats will provide an efficient reserve network for tiger conservation to maintain the evolutionary potential of Amur tigers facing environmental changes.

[Effect of VEGF-B on neuroprotection in mouse retinal ganglion cells].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor-B (VEGF-B) in retina and its effect on neuroprotection in mouse retinal ganglion cells (RGCs). METHODS: It was a experimental study. 35 of C57BL/6 mice (adult male) were used. Optic nerve crush injury was made in 28 mice, 7 as control. Expression of VEGF-B in retina was detected by hybridization in situ in each group of 2 at 6 hours, 1 day, 1 and 2 weeks after optic nerve crush. A quantitative analysis of VEGF-B mRNA was determined by real time reverse transcription polymerase chain reaction (RT-PCR) in each group of 5 at 6 hours, 1 day, 1 and 2 weeks after optic nerve crush. Additional 36 mice were divided into 4 groups: control (8), optic nerve crush (9), optic nerve crash plus PBS intravitreal injection (7), and optic nerve crash plus VEGF-B (450 mg/L) intravitreal injection (12). RGCs were counted by retrograde tracing of Fluorogold to evaluate the effect of VEGF-B on neuroprotection by microscope. RESULTS: Compared with control group, the expression of VEGF-B was significantly increased in the retina of mice and peaked at one week after the optic nerve crush. The number of RGCs was 1.7 fold higher in optic nerve crush alone and 1.9 fold higher in optic nerve crush combined with intravitreal injection of VEGF-B, which reached statistically significance (t = 0.001, P < 0.01 and t = 0.001, P < 0.01, respectively). CONCLUSIONS: Our results indicate that VEGF-B is involved in the retinal recovery processes and plays a potent role of neuroprotection in RGCs after the optic nerve crush.

Effects of Mind-Body Exercises on Cognitive Function in Older Adults: A Meta-Analysis.

BACKGROUND/OBJECTIVES: Mind-body exercise has positive effects on cognitive performance, according to clinical observation and experts' recommendations. However, its potential benefits for the cognitive function of aging adults are uncertain and still lack systematic estimations. Therefore, we conducted a systematic review and meta-analysis to evaluate the overall efficacy and effectiveness of mind-body exercises for cognitive performance in aging individuals with or without cognitive impairment. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: We searched related trials through June 2018 from four databases: Medline, Embase, PsycINFO (all via Ovid), and the Cochrane Library/Central Register of Controlled Trials. MEASUREMENTS: Methodological quality was assessed using the Cochrane Risk of Bias Tool. A meta-analysis of comparative effects was performed using Review Manager v.5.3 software, and publication bias was examined using Egger's test. RESULTS: A total of 32 randomized controlled trials with 3624 participants were ultimately included in this meta-analysis. The results revealed that mind-body exercises as a whole had benefits in improving global cognition compared with that of the control group (mean difference [MD] = 0.92; 95% confidence interval [CI] = 0.33-1.51; p = .002) and were more effective than control interventions in promoting cognitive flexibility (MD = -8.80; 95% CI = -15.22 to -2.38; p = .007), working memory (MD = 0.32; 95% CI = 0.01-0.64; p = .05), verbal fluency (standardized mean difference [SMD] = 0.27; 95% CI = 0.09-0.45; p = .003), and learning (SMD = 0.24; 95% CI = 0.10-0.39; p = .001) on cognitively intact or impaired older adults. In dose-subgroup analysis, only moderate exercise intensity (60-120 min per week) significantly increased global cognition scores compared with those of the control group (MD = 1.15; 95% CI = 0.34-1.97; p = .006). CONCLUSION: Mind-body exercises, especially tai chi and dance mind-body exercise, are beneficial for improving global cognition, cognitive flexibility, working memory, verbal fluency, and learning in cognitively intact or impaired older adults. Moderate intensity is recommended as the optimal dose for older adults. J Am Geriatr Soc 67:749-758, 2019.

Research on the anti-tumor effect of nordihydroguaiaretic acid targeting MyD88 / 药学学报

This study mainly explores the role of myeloid differentiation primary response protein 88 (MyD88) in tumorigenesis and development, to identify active compounds targeting MyD88. CRISPR/Cas9 system and xenograft tumor model were used to detect the effect of MyD88 deletion on tumor growth, and the experimental animal ethics review number was PZSHUTCM200828006. Microscale thermophoresis technology (MST) was used to identify compounds directly bind to MyD88 and further detect the impact of candidate small molecules on cell proliferation. Results showed that depletion of MyD88 significantly inhibited xenograft tumor growth of colon cancer, pancreatic cancer and skin cancer and the activity of NF-κB signaling pathway. MST showed that nordihydroguaiaretic acid (NDGA) bound to MyD88, with the binding dissociation constant Kd of 14.61 µmol·L-1. NDGA inhibited NF-κB reporting system activation and phosphorylation of p65, the key factor in NF-κB signal pathway. In addition, the results of colony formation assay showed that NDGA suppressed the proliferation of tumor cells. The above results show that, MyD88 is a potential therapeutic target for colon cancer, pancreatic cancer and skin cancer, NDGA directly binds to MyD88 and inhibits the activity of NF-κB signaling pathway, as well as inhibits the proliferation of pancreatic cancer, skin cancer and colon cancer cells.

Changes of microvascular structure in the macular region of pediatric uveitis / 中华眼底病杂志

Objective:To observe and analyze the macular microvascular system changes in unilateral pediatric uveitis (PU) and healthy contralateral eyes.Methods:A cross-sectional case-control study. From January 2019 to July 2021, 21 eyes of 21 patients with PU diagnosed in one eye (PU group), 21 unaffected contralateral eyes (contralateral eye group), and 21 age-matched volunteers with 21 eyes (NC group) during the same period were examined in Peking Union Medical College Hospital. Optical coherence tomography angiography was used to scan the 6 mm × 6 mm fundus macular area in the three groups of selected eyes to measure the vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the retina, the area of the avascular zone (FAZ) in the fovea of the macula, the choroidal thickness under the fovea (SFCT), and the retinal thickness in the fovea of the macula (CRT). The device comes with a software choriocapillary flow measurement tool, which can obtain the macula's choriocapillary density (CCD) with the fovea as the center and the diameter of the annular area of 1.0 mm, 1.5 mm, and 3.0 mm, respectively. They were recorded as CCD-1.0, CCD-1.5, and CCD-3.0. The measurement data of multiple groups were compared by analysis of variance; if the variance of the three groups of data was not uniform, the Kruskal-Wallis test was used. Multiple linear regression analysis was used to evaluate the potentially related factors of CCD.Results:Compared with the contralateral eye group and the NC group, the vessel density of SCP ( H=-13.857,-25.500; P=0.043, P<0.001), DCP ( H=-15.333, -31.595; P=0.007, P<0.001) and CCD-1.0 ( H=-14.000,-16.214; P=0.040, 0.012) of the clinically quiescent PU group were significantly decreased. CRT and FAZ were not statistically different between PU and NC groups ( F=0.955; P=1.000, 0.661). Compared with the NC group, the mean vessel density of SCP and DCP in the contralateral eye group decreased, and the difference in DCP vessel density was statistically significant ( H=-16.262, P=0.004). There was no statistically significant difference between the CCD of two groups ( P=1.000). The SFCT of the PU group was significantly thicker than that of the NC group ( F=5.552, P=0.004), however, difference was not statistically significant from the fellow eye group ( F=5.552, P=0.270). The results of multiple linear regression analysis revealed that the CCD-1.0, CCD-1.5, and CCD-3.0 showed a linear correlation with the area of FAZ ( β=-0.494, -0.527, -0.566; P=0.015, 0.009, 0.010) and CRT ( β=-0.322, -0.466, -0.342; P=0.026, 0.002, 0.028). CCD-1.0 and CCD-1.5 showed a linear correlation with the vessel density of DCP ( β=0.277, 0.275; P=0.047, 0.045). Conclusion:Both retinal and choroidal microvasculature are abnormal in resting eyes with PU, and macular circulation disorders may be present in the unaffected fellow eye.

The Response of Photosynthetic Functions of F1 Cutting Seedlings From Physocarpus amurensis Maxim (♀) × Physocarpus opulifolius "Diabolo" (♂) and the Parental Seedlings to Salt Stress.

This paper selected clonal cutting seedlings from the F1 hybrid varieties of Physocarpus amurensis Maxim (♀) × P. opulifolius "Diabolo" (♂) as research material to study the response of the photosynthetic gas exchange parameters and chlorophyll fluorescence parameters of P. amurensis hybrids and their parental leaves to NaCl stress (with concentrations of 0, 50, 100, and 200 mmol⋅L-1). The results showed that under salt stress, the stomatal conductance (Gs), transpiration rate (Tr), and net photosynthetic rate (Pn) of the three kinds of P. amurensis all significantly decreased. When the NaCl concentration was below 100 mmol⋅L-1, the intercellular CO2 concentration (Ci) of leaves of the three samples declined with the increase of salt concentration; however, when the concentration increased to 200 mmol⋅L-1, Ci did not decrease significantly, especially when the Ci of P. opulifolius "Diabolo" presented a slight increase. This indicated that the decline of photosynthetic carbon assimilation capacity induced by salt stress was the consequence of interaction between stomatal factors and non-stomatal factors, and the stomatal factors played an important role when the salt concentration was below 200 mmol⋅L-1. Compared with P. amurensis, the photosynthetic gas exchange capability of P. opulifolius "Diabolo" leaves was more sensitive to salt stress, and the limitation of non-stomatal factors was relatively evident. However, the photosynthetic capacity of hybrid P. amurensis leaves with the desired purple color was improved compared with P. amurensis. Under salt stress, the PSII activity of the three kinds of P. amurensis leaves declined, the electron transfer was inhibited, and obvious signs of photoinhibition were present. The PSII activity of P. opulifolius "Diabolo" leaves was more sensitive to salt stress than that in P. amurensis. Under salt stress, the NPQ of P. opulifolius "Diabolo" leaves decreased greatly, while under high salt concentrations the degree of photoinhibition in P. amurensis and hybrid P. amurensis were reduced due to a relatively high NPQ. With the increase of salt concentration, the Vk of P. amurensis and hybrid P. amurensis leaves presented a decreasing trend. However, the Vk of P. opulifolius "Diabolo" leaves increased slightly. This suggested that the effects of salt stress on the oxygen-evolving complex (OEC) of the three P. amurensis sample types were relatively limited and only the OEC of P.s opulifolius "Diabolo" leaves were slightly sensitive to salt stress. The VJ of all leaves from the three P. amurensis types increased under salt stress, and the VJ increased significantly when the salt concentration increased to 200 mmol⋅L-1, indicating that salt stress obviously impeded the electron transfer chain from QA to QB on the PSII receptor side. Moreover, high salt concentrations caused thylakoid membrane dissociation. The electron transfer and degree of damage to the thylakoid membrane of P. opulifolius "Diabolo" leaves were obviously higher than that of P. amurensis. However, the electron transfer capacity on the PSII receptor side as well as the degree of damage of the thylakoid membrane of hybrid P. amurensis leaves was obviously lower than those of P. opulifolius "Diabolo." The salt tolerance of photosynthetic functions of hybrid P. amurensis (♀) × P. opulifolius "Diabolo" (♂) leaves was improved compared with that of parental P. opulifolius "Diabolo," and the hybrid shows obvious hybrid vigor for photosynthesis.

Heliangin acts as a covalent ligand of RPS2 that disrupts pre-rRNA metabolic processes in NPM1-mutated acute myeloid leukemia

Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.

Association between low ambient temperature during pregnancy and adverse birth outcomes: A systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein.@*METHODS@#Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis.@*RESULTS@#A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04-1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03-1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99-5.38).@*CONCLUSIONS@#Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors.@*REGISTRATION@#No. CRD42021259776 at PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ).

Adult cerebral hepatolenticular degeneration: report of one case with literature review / 中华全科医师杂志

A 26-year-old male presented with tremor of bilateral shoulders and hands as the major symptom and also had cognitive and emotional abnormalities for more than 1 year, who was diagnosed as cerebral hepatolenticular degeneration (HLD) in Tongji Hospital of Huazhong University of Science and Technology in October 2021. The serum ceruloplasmin and urine copper levels of the patient were 0.023 g/L and 3760.00 μg/24 h, respectively, and the Kayser-Fleischer (K-F) ring was seen in the cornea. Genetic testing revealed a homozygous mutation of ATP7B gene c.2975C>T (p.Pro992Leu), while transcranial sonography (TCS) showed lenticular nucleus hyper-echogenicity. The literature was searched using hepatolenticular degeneration and transcranial sonography as key words; and 9 articles involving 150 HLD cases were obtained. The lenticular nucleus hyper-echogenicity was presented in 76.9% HLD patients (150/195), while only in 12.7% healthy subjects (17/134) ( P<0.001), suggesting that advanced transcranial sonography can detect the metal deposition and may be used for diagnosis of cerebral HLD.

Cinobufagin disrupts mitosis and microtubule polymerization via targeting KATNB1 in cancer cells / 药学学报

Huachansu is a traditional Chinese medicine widely used in the clinic for cancer therapy, while the underlying mechanism is not fully clarified. This study was to investigate the targets and mechanisms of cinobufagin (CBG), an active component of Huachansu, in terms of blocking mitosis of cancer cells. Propidium iodide (PI) DNA staining was used to analyze the effect of CBG on cell cycle. The effect of CBG on mitosis of cancer cells was examined by α-tubulin and pericentrin staining after synchronization by a double thymidine block. Tubulin turbidity, tubulin polymerization and α‍-tubulin immunofluorescence assays were used to evaluate the effect of CBG on microtubule polymerization. CRISPR/Cas9 gene-editing technology was used to knockout microtubule-severing protein Katanin regulatory subunit B1 (KATNB1) in HCT116 cells, and the inhibitory effect of CBG on wild-type cells and knockout cells was measured by CCK-8. The engagement of CBG with KATNB1 was measured by CETSA and DARTS assays. The effect of CBG on KATNB1 protein and mRNA level was examined by Western blot and real-time PCR, respectively. Our data showed that CBG arrested HCT116 cell cycle at the G2/M phase, disrupted mitosis and induced centriole overduplication. CBG significantly inhibited tubulin polymerization in vitro and in vivo. The cytotoxicity of CBG inhibition on HCT116 was significantly attenuated upon KATNB1 depletion. Moreover, CBG bound to KATNB1 and decreased its protein level, while mutated KATNB1 weakened this effect. In conclusion, CBG inhibited microtubule polymerization via targeting KATNB1, thereby disrupting mitosis in cancer cells.

Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.@*METHODS@#This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.@*RESULTS@#A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.@*CONCLUSIONS@#In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Grading of Seed Rhizoma for Curcuma phaeocaulis and Its Effect on Plant Growth， Yield and Quality of Medicinal Materials / 中国实验方剂学杂志

Objective:To establish the grading standard of <italic>Curcuma phaeocaulis</italic> seed rhizoma，and explore the effect of seed rhizoma classification on the growth，yield and quality of <italic>C. phaeocaulis</italic>. Method:The purity，diameter，weight，length，germination rate and water content of <italic>C. phaeocaulis</italic> seed rhizoma samples were determined. The grading index was determined by partial correlation analysis，variance analysis and cluster analysis. According to actual conditions of production，the classification standard of<italic> C. phaeocaulis</italic> seed rhizoma was established. Then the field experiments were carried out with different grades of seed rhizoma for treatment， so as to analyze the effect of seed rhizoma grade on plant growth，yield and quality of medicinal materials. Result:With seed rhizoma diameter and seed rhizoma weight as classification indexes，<italic>C. phaeocaulis</italic> seed rhizoma were divided into three grades. The field experiments showed that with the growth and development of <italic>C. phaeocaulis</italic>，there were significant differences in plant height and leaf length among different grades of seed rhizoma during the root tuber expansion period （<italic>P</italic><0.05）. The yield of Curcumae Radix and Curcumae Rhizoma produced by different grades of seed rhizoma was in the order of first-class ginger>second-class ginger>third-class ginger>substandard seed rhizoma. According to the analysis of the proportion of the commodity grade of medicinal materials，the higher the grade of seed rhizoma was，the higher the proportion of the first-grade Curcumae Radix occupied. According to the analysis of the quality of medicinal materials，there was no significant difference in the content of extract，volatile oil and germanone in Curcumae Radix and Curcumae Rhizoma produced by different grades of seed rhizoma. Conclusion:The grading standard of seed rhizoma was established based on the systematic study on the classification method of <italic>C. phaeocaulis</italic> seed rhizoma. According to the field experiment， grading planting of seed rhizoma can promote plant growth and development，increase the yield of medicinal materials，and improve the proportion of first-grade medicinal materials， with no impact on the internal quality of medicinal materials. Therefore， classification of <italic>C. phaeocaulis</italic> seed rhizoma is scientific and necessary，and can lay the foundation for the standardized cultivation of <italic>C. phaeocaulis</italic>.