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Background Herpes zoster presents as clustered blisters on one side of the body, accompanied by nerve pain. This is caused by reactivation of the varicella zoster virus, and it occurs primarily in people with weakened immunity. Tumor and chemotherapy drugs can impair the patient's immune function, induce herpes zoster and prolong the course of disease.In these patients, skin changes can last for months and blisters can recur and cause serious complications such as postherpetic neuralgia.Acupuncture is a common alternative therapy for herpes zoster in East Asia. Case presentation We report a case of an elderly male patient with widespread herpes zoster in the trunk after non-Hodgkin's lymphoma chemotherapy. The patient had received conventional treatment with valaciclovir and mecobalamin within 24 hours of symptom onset. Because neither the clustered blisters nor the nerve pain were improved a week later, acupuncture and related techniques were applied. These included electro-acupuncture, surrounding acupuncture, fire acupuncture, and cupping. The patient recovered 20 days after the herpes zoster attack, and there were no adverse reactions during the treatment process. Conclusions This case suggests that acupuncture and related techniques are effective interventions for this condition.This case report is innovative because it shows that acupuncture as an adjuvant treatment can improve the skin lesions in patients with HZ after tumour chemotherapy, relieve pain, and shorten the course of HZ.

Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin‐1, an actin‐binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin‐1 in ADMA‐induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty‐two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin‐1 small hairpin RNA to interrupt the expression of profilin‐1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin‐1 was tested using real‐time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin‐1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p

HSR studies have been one of the most important issues in economic geography, transport economics and policy. However, prior studies give rare attention to its role on the technological innovation collaboration, which become increasing important nowadays. Using co-patent data of the State Intellectual Property Office (SIPO) database from 2000 to 2016, this paper investigates the role of HSR services in cross-city technological innovation collaboration. Empirical results show: 1) the intensity of cross-city technological innovation collaboration activities remains at a low level before the debut of HSR services in China, and the difference on this indicator between cities with and without HSR services is statistically insignificant. With the emergence of HSR network, cross-city innovation collaboration is booming and cities with and without HSR services show distinct trends. 2) HSR services play a significant positive role in stimulating the intensity of cross-city technological innovation collaboration activities of HSR cities. 3) megacities benefit most from the HSR network, and secondary cities also benefit from being connected to megacities by HSR lines. 4) The travel time between city pairs is significantly correlated with the intensity of collaborative innovation activities. Our results suggesting interregional innovation bonds, which implicitly featuring the channel of knowledge flow, are established or strengthened by high-speed transport investments.

OBJECTIVE To study the association of hyperuricaemia with clinical and pathological characteristics of patients with IgA nephropathy, and to clarify adverse effects of hyperuricaemia on the onset and progression of IgA nephropathy. METHODS A total of 244 patients with IgA nephropathy enrolled in Jiangjin Center Hospital were divided into a group with normal serum uric acid level and a group with elevated level. Age, gender, course of disease, blood pressure, liver function, renal function, blood lipid levels, blood glucose level, 24-hour urine protein level and pathological grades were recorded. The correlations of serum uric acid level with clinical indices and pathological grades were analyzed. RESULTS The incidence rate of IgA nephropathy complicated with hyperuricaemia was 25.4%. The two groups had significantly different course of disease, body mass index (BMI), and levels of urea nitrogen, creatinine, triglyceride and urine protein (p

Objective This study aimed to investigate the protective effect of astragalus–saffron–rhubarb mixture (Bao’shen recipe, BSR) on diabetic nephropathy (DN) in db/db mice and preliminarily explore the possible underlying mechanism. Methods A total of 125 8-week-old male db/db mice with DN were randomly divided into five groups: model group, irbesartan group and high-, medium- and low doses of BSR group, while 25 male db/m mice were used as a blank control. At 8, 12, 16, 20, and 24 weeks of feeding, the animals were sacrificed and blood as well as urine samples were collected for blood glucose, urea nitrogen, creatinine and urinary albumin excretion rate (UAER) measurement via blood glucose meter or corresponding detection kits, respectively. The renal tissues of each mouse underwent hematoxylin and eosin (H&E), Masson, periodic acid Schiff (PAS) staining. Renal homogenate was used to detect IL-6, TNF-α, TNF-1R and TNF-2R by enzyme-linked immunosorbent assay. Additionally, the data obtained was statistically analyzed via one-way analysis of variance. Results BSR could effectively reduce the body weight, blood glucose, UAER, blood urea nitrogen and creatinine levels, relieve the proliferation of mesangial tissue, and lower the levels of IL-6, TNF-α, TNF-1R, and TNF-2R in renal tissue of db/db mice with DN. Of note, the high-dose BSR treatment group has advantages over irbesartan treatment group in improving above-mentioned aspects. Conclusion BSR could effectively delay the progress of DN, partly related to its anti-inflammation effect.

Background Surgery is the primary treatment for locally advanced thyroid cancer. For some cases, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an opt...

Background : Platelet distribution width (PDW) and PDW-to-platelet ratio (PPR) have been proven to be good prognostic indicators for many diseases. However, their prognostic values in severe burns have not been reported. Objective : To investigate the early time course of PDW and PPR in severe burn patients and investigate their prognostic values. Methods : This is a 16-year, single-center retrospective study of 590 severe burn patients. The complete blood count parameters on day 1, day 3 and day 7 postburn, including PDW and PPR, were collected. Receiver operating characteristic curves (ROC) analysis, multiple logistic regression analysis and Kaplan-Meier survival analysis were performed to evaluate the prognostic values of PDW and PPR in severe burn patients. Results : According to 120-day follow-up records, 96 patients were non-survivors and 494 patients were survivors. ROC and area under the curve (AUC) analysis showed that, for predicting 120-day prognosis, the AUC of PDW (0.782) and PPR (0.816) on day 3 was the highest, followed by the AUC of PDW (0.764) and PPR (0.750) on day 7. The ROC-AUC of PPR (0.816) on day 3 was very close to that of the ABSI score (0.818). Multiple logistic regression analysis showed that the PDW (P = 0.033 and P = 0.009) and PPR (P = 0.052 and P = 0.046) on day 3 and day 7 were all significantly independently positively associated with 120-day mortality. Kaplan-Meier survival analysis showed that high PDW and PPR were both significantly associated with a high 120-day mortality rate on day 3 and day 7. Conclusion : PDW and PPR on day 3 and day 7 were independent risk factors for 120-day mortality in severe burn patients. These objective and readily available prognostic indicators may be more clinically favored.

In this review, we highlight our recent developments on the formic acid refining of lignocellulosic biomass and how it can be an innovative way to produce sustainable hydrogen and fuels. There is a worldwide high demand for green energy and green chemistry endeavors to drastically slow down climate change in accord with the COP 21. This review mainly focuses on the deconstruction of the lignocellulosic biomass, using formic acid-based mixtures, into its 3 main components and how they can be the new resources for hydrogen, fuels, and products in the 21st century. We are underlining the natural carbon capture in the form of atmospheric CO2 concentrated into lignocellulosic biomass wastes from the forest and agricultural land sites and the subsequent low energy organic extraction of cellulose, lignin, and hemicelluloses. We illustrate in this review that our dependence on fossil fuels will be greatly reduced, and that atmospheric CO2, sunlight and water will provide safe energy and products for future generations.

BACKGROUND Hypereosinophilia (HE) is defined as a peripheral blood eosinophil count of > 1.5 × 109/L and may be associated with tissue damage. The clinical presentations of HE vary; however, myocardial fibrosis and thrombosis can threaten the lives of patients with sustained eosinophilia. Cerebral venous sinus thrombosis (CVST) in the setting of eosinophil-related diseases has seldom been reported. Here, we review the literature on HE with CVST to increase knowledge and encourage early diagnosis. CASE SUMMARY A previously healthy 41-year-old man was admitted to hospital with diarrhea and abdominal pain. He was treated with antibiotics for suspected acute colitis. Three days later, he experienced headache and vomiting. Brain computed tomography (CT) revealed thrombosis of the left jugular vein to the left transverse sinus vein. Platelet (PLT) count decreased to 60 × 1012/L, and absolute eosinophil count (AEC) increased to 2.41 × 109/L. He was treated with low-molecular-weight heparin. PLT count progressively decreased to 14 × 109/L, and we terminated anticoagulation and performed PLT transfusion. Six days after admission, he complained of a worsening headache. Brain CT revealed right temporal lobe and left centrum semiovale intracerebral hemorrhage, and AEC increased to 7.65 × 109/L. We used prednisolone for HE. The level of consciousness decreased, so emergency hematoma removal and decompressive craniectomy for right cerebral hemorrhage were performed. The patient was alert 2 d after surgery. He was treated with anticoagulation again 2 wk after surgery. Corticosteroids were gradually tapered without any symptomatic recurrence or abnormal laboratory findings. CONCLUSION HE can induce CVST, and we need to focus on eosinophil counts in patients with CVST.

Purpose The aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery. Methods A total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Nomograms and risk stratification models were constructed. Results Patients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668–0.843], P, Graphical abstract Image 1, Highlights • The effect of surgery in older patients with stage IV breast cancer (BC) is discussed. • The proportion of older patients with stage IV BC who underwent surgery declined. • A specific group of older patients with stage IV BC can benefit from surgery. • Nomograms can be used to predict the prognosis of older patients with stage IV BC.

Objective This research was performed to investigate the correlation between acute kidney injury (AKI) and systemic immune-inflammation index (SII) in severe acute pancreatitis (SAP) patients. Methods The study included 218 SAP patients from Chongqing Jiangjin Center Hospital during January 2016 to October 2020. The SII was defined as platelet × neutrophil/lymphocyte ratio. After univariate analysis, logistic regression analysis was used for analyzing independent risk factors of AKI in SAP patients. Receiver operating characteristic (ROC) curve was used for analyzing the prognostic value of the SII. Results AKI occurred in 74 cases and its incidence rate was 33.9%. The median SII value of AKI patients was higher than that of patients without AKI. After multivariate analysis, SII, age, triglyceride (TG), neutrophil ratio (NEU-R), C-reactive protein (CRP), aspartate aminotransferase (AST), and serum albumin (ALB) were independent predictors of AKI. Serum ALB was an independent protective factor. The optimum threshold truncation value of SII was 2880.1*10^9/L. Compared with other inflammatory factors, SII had a better prediction efficiency. Conclusion The SII, TG, NEU-R, CRP, and ALB were significant independent predictors of AKI in SAP patients. Serum TG, NEU-R, CRP, and SII were risk factors. Serum ALB was a protective factor. The SII may be a novel, simple, and strong marker for the accurate early prediction of AKI in SAP patients.

Background Hemichorea usually results from vascular lesions of the basal ganglia. Most often, the lesion is contralateral to the affected limb but rarely, it may be ipsilateral. The pathophysiology of ipsilateral hemichorea is still poorly understood. We review the literature on hemichorea due to ipsilateral cerebral infarction and explore possible mechanisms for its occurrence. Case summary A 72-year-old woman presented with complaints of involuntary movements of the muscles of the left side of the face and mild weakness of the right limbs. Her symptoms had started suddenly 1 d earlier. After admission to the hospital, the involuntary movements spread to involve the left limbs also. Magnetic resonance imaging revealed a left thalamic infarction. The patient's hemichorea subsided after treatment with haloperidol (2 mg per time, 3 times/d) for 3 d; the hemiparesis resolved with rehabilitation physiotherapy. She is presently symptom free and on treatment for prevention of secondary stroke. We review the literature on the occurrence of ipsilateral hemichorea following thalamic infarction and discuss the possible pathomechanisms of this unusual presentation. Conclusion Ipsilateral hemichorea following a thalamic stroke is rare but it can be explained by structure of the extrapyramidal system. The thalamus is a relay station that exerts a bilateral control of motor function.

Background Brugada syndrome (BrS) is an inherited disease characterized by an electrocardiogram (ECG) with a coved-type ST-segment elevation in the right precordial leads (V1-V3), which predisposes to sudden cardiac death (SCD) due to polymorphic ventricular tachycardia or ventricular fibrillation in the absence of structural heart disease. We report the case of a 29-year-old man with out-of-hospital cardiac arrest. BrS is associated with a high incidence of SCD in adults, and increasing the awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving. Case summary A 29-year-old man suffered from out-of-hospital cardiac arrest, and after defibrillation, his ECG demonstrated a coved-type elevated ST segment in V1 and V2. These findings were compatible with type 1 Brugada pattern, and ECG of his brother showed a type 2 Brugada pattern. The diagnosis was BrS, NYHF IV, multiple organ dysfunction syndrome, sepsis, and hypoxic ischemic encephalopathy. The patient had no arrhythmia episodes after discharge throughout a follow-up period of 36 mo. Conclusion Increasing awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving.

To explore whether acupuncture can improve sleep disturbance, cognitive impairment and emotional disorders caused by sleep deprivation, and its association with the attenuation of oxidative stress injury in prefrontal cortex. Fifty-two male Sprague-Dawley rats were randomly divided into a control group (n=10), a model group (n=14), a manual acupuncture (MA) group (n=14), and a sham-MA group (n=14). All the groups were established as sleep deprivation models via the modified multiple platform method, except for the control group. Rats in both the MA group and the sham-MA group received corresponding intervention, respectively. After modeling and intervention, the four groups received three behavioral tests, namely sleep monitoring, by comprehensive lab animal monitoring system (CLAMS), Morris water maze (MWM) test and open-field test (OFT), followed by oxygen free radical level test and Western blot (WB) detection for the expression levels of Bax and Bcl-2. The MA group derived more sleep time within 24 h than either the model group or the sham-MA group (both P 0.05), and the escape latency was significantly shorter in these three groups than that in the model group (all P

BACKGROUND Floating elbow along with ipsilateral multiple segmental forearm fracture is a rare and high-energy injury, although elbow dislocation or fracture of the ulna and radius may occur separately. CASE SUMMARY We report the case of a 37-year-old woman with open (IIIA) fracture of the right distal humerus with multiple shaft fractures of the ipsilateral radius and ulna with a history of falling from a height of almost 20 m from a balcony. After providing advanced trauma life support, damage control surgery was performed to debride the arm wound and temporarily stabilize the right upper limb with external fixators in the emergency operating room. Subsequently, one-stage internal fixation of multiple fractures was performed with normal values of biochemical indicators and reduction in limb swelling. The patient achieved good outcome at the 7 mo follow-up. CONCLUSION One- or two-stage treatment must be performed according to the type of injury; we efficiently used the “damage control principle.”

Volatilization loss of molybdenum trioxide (MoO3) always takes place during the synthesis of Mo-containing alloying steel in the steelmaking process. In this work, the sublimation kinetics and mechanism of MoO3 in the range of 1273 to 1373 K were analyzed, in which the methods of model fitting, FE-SEM, EDS, and thermodynamic calculation were adopted. The results showed that sublimation of high-purity MoO3 (defined as the case III) and industrial grade MoO3 with the thickness of 3 mm (defined as the case II) were mainly controlled by the chemical reaction on the surface; increasing the thickness of industrial grade MoO3 to 7 mm (defined as the case I), the diffusion model was obeyed, instead. Activation energies of the three cases were extracted to be 127.489 (case III), 197.418 (case II), and 89.76 kJ/mol (case I), respectively. With the adoption of lever principle, the weight ratio of melting (from solid to liquid) to vaporization (from liquid to gas) during the whole volatilization process was estimated, i.e., 2.52:1 for case III, 0.84:1 for case II, and 5.89:1 for case I. The possible sublimation mechanism of industrial grade MoO3 was also proposed.

Background Nonketotic hyperglycemia (NKH) is characterized by hyperglycemia with little or no ketoacidosis. Diverse neurological symptoms have been described in NKH patients, including choreoathetosis, hemiballismus, seizures, and coma in severe cases. Homonymous hemianopia, with or without occipital seizures, caused by hyperglycemia is less readily recognized. Case summary We describe a 54-year-old man with NKH, who reported seeing round, colored flickering lights with right homonymous hemianopia. Cranial magnetic resonance imaging demonstrated abnormalities in the left occipital lobe, with decreased T2 signal of the white matter, restricted diffusion, and corresponding low signal intensity in the apparent diffusion coefficient map. He responded to rehydration and a low-dose insulin regimen, with improvements of his visual field defect. Conclusion Patients with NKH may present focal neurologic signs. Hyperglycemia should be taken into consideration when making an etiologic diagnosis of homonymous hemianopia.

Visual background extraction algorithm (ViBe) uses the first frame image to initialize the background model, which can easily introduce the “ghost”. Because ViBe uses the fixed segmentation threshold to achieve the foreground and background segmentation, the detection results in many false detections for the highly dynamic background. To solve these problems, an improved ghost suppression and adaptive Visual Background Extraction algorithm is proposed in this paper. Firstly, with the pixel’s temporal and spatial information, the historical pixels of a certain combination are used to initialize the background model in the odd frames of the video sequence. Secondly, the background sample set combined with the neighborhood pixels are used to determine a complex degree of the background, to acquire the adaptive segmentation threshold. Thirdly, the update rate is adjusted based on the complexity of the background. Finally, the detected result goes through a post-processing to achieve better detection results. The experimental results show that the improved algorithm will not only quickly suppress the “ghost”, but also have a better detection in a complex dynamic background.

Coronary artery spasm can cause recurrent variant angina with ST-segment elevation. The patient was asymptomatic with normal vitals and ECG was normal. We present a case associated with transient ST-segment elevation and significant increase in troponin levels with non-critical lesion with normal CAG.

Background and objectives Haemovigilance involves surveillance of the whole chain of blood transfusion with the aim of identifying adverse events and errors and improving outcomes for patients. The Chinese Haemovigilance Network, founded in August 2017, has witnessed a rapid development in the last three years. Materials and methods Based on the 1,022 cases in 2019, we analysed the adverse reactions (ARs) by blood component, clinical outcome severity and demography of recipients in an effort to publish the first annual Chinese haemovigilance report. Results The AR rate associated with blood transfusion in 2019 was 0·2% in China. Allergic reactions and FNHTR were the two most common adverse symptoms, accounting for 97·7% of the reports. Two-thirds of the TAD, AHTR and TACO and all of the HTR and DHTR resulted in hospitalization or prolongation of hospitalization. Plasma and AP were usually associated with allergic reaction (81·1%), whereas red cells more commonly cause FNHTR (68·8%) and all the AHTR, HTR, DSTR and DHTR. 84·1% of patients were aged 16 years or over, and the majority of the TAD, AHTR, TACO and HTR involved patients aged 60 and above. The ratio of serious adverse reactions (SARs) was 8·2%. Allergic reaction and FNHTR were top two (85·7%) SARs. The first case related to anti-D immunoglobulin was detected in a DHTR report. Conclusion This report provides the world's first overview of transfusion-related adverse reactions in China. This report is useful for better understanding transfusion risks in China.

BACKGROUND Intrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood. AIM To investigate the link between the gut microbiota and serum metabolome in ICP patients. METHODS In this study, a total of 30 patients were recruited, including 15 patients with ICP (disease group) and 15 healthy pregnant patients (healthy group). The serum nontarget metabolomes from both groups were determined. Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups. By comparing the differences in the microbiota and metabolite compositions between the two groups, the relationship between the gut microbiota and serum metabolites was also investigated. RESULTS The Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis, bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls. In addition, some pathways related to protein metabolism were also enriched in the ICP patients. The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition (beta diversity) between the ICP patients and healthy controls. At the phylum level, we observed that the relative abundance of Firmicutes was higher in the healthy group, while Bacteroidetes were enriched in the disease group. At the genus level, most of the bacteria depleted in ICP are able to produce short-chain fatty acids (e.g., Faecalibacterium, Blautia and Eubacterium hallii), while the bacteria enriched in ICP are associated with bile acid metabolism (e.g., Parabacteroides and Bilophila). Our results also showed that specific genera were associated with the serum metabolome. CONCLUSION Our study showed that the serum metabolome was altered in ICP patients compared to healthy controls, with significant differences in the bile, taurine and hypotaurine metabolite pathways. Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota, which may further affect the course of progression of ICP.

Background: Cardiac hypertrophy is a key biological response to injurious stresses such as pressure overload and, when excessive, can lead to heart failure. Innate immune activation by danger signals, through intracellular pattern recognition receptors such as nucleotide-binding oligomerization domain 1 (Nod1) and its adaptor receptor-interacting protein 2 (RIP2), might play a major role in cardiac remodeling and progression to heart failure. We hypothesize that Nod1/RIP2 are major contributors to cardiac hypertrophy, but may not be sufficient to fully express the phenotype alone. Methods: To elucidate the contribution of Nod1/RIP2 signaling to cardiac hypertrophy, we randomized Nod1 –/– , RIP2 –/– , or wild-type mice to transverse aortic constriction or sham operations. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice. Results: Nod1 and RIP2 proteins were upregulated in the heart after transverse aortic constriction, and this was paralleled by increased expression of mitochondrial proteins, including mitochondrial antiviral signaling protein (MAVS). Nod1 –/– and RIP2 –/– mice subjected to transverse aortic constriction exhibited better survival, improved cardiac function, and decreased cardiac hypertrophy. Downstream signal transduction pathways that regulate inflammation and fibrosis, including NF (nuclear factor) κB and MAPK (mitogen-activated protein kinase)-GATA4/p300, were reduced in both Nod1 –/– and RIP2 –/– mice after transverse aortic constriction compared with wild-type mice. Coimmunoprecipitation of extracted cardiac proteins and confocal immunofluorescence microscopy showed that Nod1/RIP2 interaction was robust and that this complex also included MAVS as an essential component. Suppression of MAVS expression attenuated the complex formation, NF κB signaling, and myocyte hypertrophy. Interrogation of mitochondrial function compared in the presence or ablation of MAVS revealed that MAVS serves to suppress mitochondrial energy output and mediate fission/fusion related dynamic changes. The latter is possibly linked to mitophagy during cardiomyocytes stress, which may provide an intriguing link between innate immune activation and mitochondrial energy balance under stress or injury conditions. Conclusions: We have identified that innate immune Nod1/RIP2 signaling is a major contributor to cardiac remodeling after stress. This process is critically joined by and regulated through the mitochondrial danger signal adapter MAVS. This novel complex coordinates remodeling, inflammatory response, and mitochondrial energy metabolism in stressed cardiomyocytes. Thus, Nod1/RIP2/MAVS signaling complex may represent an attractive new therapeutic approach toward heart failure.

BACKGROUND Cerebrotendinous xanthomatosis (CTX) is a treatable autosomal recessive inherited metabolic disorder. It results from a deficiency of sterol 27-hydroxylase (CYP27A1), which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis. Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain, eyes, tendons, and vessels, resulting in juvenile cataracts, tendon xanthoma, chronic diarrhea, cognitive impairment, ataxia, spastic paraplegia, and peripheral neuropathy. CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports. CASE SUMMARY A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy. CONCLUSION CYP27A1 genetic analysis should be the definitive method for CTX diagnosis. This case suggests that urinary system diseases may be neglected in CTX patients. The clinical, biological, radiological, and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.

Cocaine abuse continues to be a serious health problem worldwide. Despite intense research, there is still no FDA-approved medication to treat cocaine use disorder (CUD). In this report, we explored the potential utility of beta-caryophyllene (BCP), an FDA-approved food additive for the treatment of CUD. We found that BCP, when administered intraperitoneally or intragastrically, dose-dependently attenuated cocaine self-administration, cocaine-conditioned place preference, and cocaine-primed reinstatement of drug seeking in rats. In contrast, BCP failed to alter food self-administration or cocaine-induced hyperactivity. It also failed to maintain self-administration in a drug substitution test, suggesting that BCP has no abuse potential. BCP was previously reported to be a selective CB2 receptor agonist. Unexpectedly, pharmacological blockade or genetic deletion of CB1, CB2, or GPR55 receptors in gene-knockout mice failed to alter BCP's action against cocaine self-administration, suggesting the involvement of non-CB1, non-CB2, and non-GPR55 receptor mechanisms. Furthermore, pharmacological blockade of μ opioid receptor or Toll-like receptors complex failed to alter, while blockade of peroxisome proliferator-activated receptors (PPARα, PPARγ) reversed BCP-induced reduction in cocaine self-administration, suggesting the involvement of PPARα and PPARγ in BCP's action. Finally, we used electrical and optogenetic intracranial self-stimulation (eICSS, oICSS) paradigms to study the underlying neural substrate mechanisms. We found that BCP is more effective in attenuation of cocaine-enhanced oICSS than eICSS, the former driven by optical activation of midbrain dopamine neurons in DAT-cre mice. These findings indicate that BCP may be useful for the treatment of CUD, likely by stimulation of PPARα and PPARγ in the mesolimbic system.

Background The effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials. However, whether higher dosage (more frequent) acupuncture can bring greater responses (a greater size of effect) is less understood. Objective This study is designed to investigate whether a five-times weekly (5 Ts/w) electroacupuncture (EA) treatment is better than a three-times weekly (3 Ts/w) EA in alleviating sleep deprivation, and sleep disturbance-induced cognitive dysfunctions and negative emotions in rats through four various behavioral tests. Methods Forty-six male Sprague-Dawley rats were randomly divided into control group (n = 10), model group (n = 12), EA-3 Ts/w group (n = 12), and EA-5 Ts/w group (n = 12). Except for the control group, the other three groups were established as chronic sleep deprivation models via the modified multi-platform water environment methodology. Then, rats in both EA-3 Ts/w group and EA-5 Ts/w group received corresponding dosage of EA therapy, respectively. After modeling and interventions, all four groups received four behavioral tests as follows: (1) sleep behavioral monitoring and evaluation was achieved by Comprehensive Lab Animal Monitoring System (CLAMS). (2) Cognitive functions were assessed by Novel Object Recognition (NOR) test. (3) Depressive-like behaviors was evaluated by Open-Field (OF) test. (4) Anxiety-like behaviors was appraised by Elevated Plus-Maze (EPM) test. After finishing the behavioral tests, the hippocampus of each rat was removed and its synaptic structure changes were observed under electron microscope. Results (1) CLAMS: two EA groups derived more sleep time within 24 h than the model group (both P 0.05). (2) NOR test: NOR ratio in the EA-3 Ts/w group was higher than that of the model group (P 0.05), although both of them were lower than that of the control group (both P 0.05) but was found in both the model group (P Conclusion (1) Five-week EA treatment can partially mitigate cognitive dysfunctions, anxiety-like behaviors, and depressive behaviors in rats with sleep deprivation, and this effect might be associated with the repairs on mitochondrial damage in hippocampal neurons. (2) There is insufficient evidence supporting 3 Ts/w EA treatment is less effective than 5 Ts/w EA treatment in mitigating sleep deprivation symptoms and depressive behaviors induced by sleep deprivation among rats. (3) 5 Ts/w EA treatment might be more effective than 3Ts/w EA treatment in attenuating sleep deprivation-induced cognitive impairments while it might further increase rat's anxiety-like behaviors at the same time.

Background and purpose Despite widespread abuse of cocaine, there are no approved treatments for cocaine use disorder. Chronic cocaine use is associated with up-regulated dopamine D3 receptor expression in the brain. Therefore, most D3 -based medication development has focused on D3 antagonists. However, D3 antagonists do not attenuate cocaine intake under "easy" self-administration conditions, when response requirements are low. We evaluated a novel, highly selective and metabolically stable D3 partial agonist, (±)VK4-40, for its efficacy in reducing cocaine intake and relapse to drug seeking. Experimental approach The impact of (±)VK4-40 on cocaine intake and relapse was evaluated using intravenous self-administration procedures under a fixed-ratio 2 reinforcement schedule and cocaine-primed reinstatement conditions in rats. Optogenetic brain-stimulation reward procedures were used to evaluate the interaction of (±)VK4-40 and cocaine in the mesolimbic dopamine system in mice. Sucrose self-administration in rats and a conditioned place preference paradigm in mice were used to evaluate the abuse potential of (±)VK4-40 alone and other unwanted effects. Key results (±)VK4-40 dose-dependently reduced cocaine self-administration and cocaine-primed reinstatement of drug-seeking behaviour. (±)VK4-40 also inhibited cocaine-enhanced brain-stimulation reward caused by optogenetic stimulation of dopamine neurons in the ventral tegmental area. (±)VK4-40 alone decreased brain-stimulation reward but produced neither conditioned place preference nor place aversion. This new D3 partial agonist also failed to alter oral sucrose self-administration. Conclusion and implications The novel D3 partial agonist, (±)VK4-40 attenuates cocaine reward and relapse in rodents, without significant unwanted effects. These findings support further investigation of D3 partial agonists as putative treatments for cocaine use disorder.

Objective Compared with Occident's data, the incidence of Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) had been reported as relatively low in Mainland China. The objective of this study was to report the integrated prevalence of HPV and Epstein‐Barr virus (EBV), and further evaluate the different behaviors of HPV‐positive and ‐negative OPSCCs in eastern China. Methods In a cohort of 170 nonmetastatic OPSCCs treated from January 2007 to July 2019, p16 protein expression, HPV genotypes, and Epstein‐Barr virus‐encoded RNA (EBER) were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). The clinical and pathologic findings were further collected and analyzed to comprehensively reveal the behaviors of Chinese OPSCCs. Results Out of the 170 tumor tissues evaluated, 57.6% (98) samples had positive p16 expressions. A total of 65.1% (99/152) samples had positive HPV genotypes, besides HPV16 (92/152), HPV11, 18, 33, 53, and 58 were also detected. The positive rate of EBER was 7.2% (9/124), and the co‐infection rate of EBV/HPV was 4.0%. Related to the unequal distributions of p16 expression, HPV‐related tumors arisen from tonsillar and non‐tonsillar accounted for 68.8% (75/109) and 37.7% (23/61) of their cases, respectively (P, HPV‐positive OPSCC in China resembled with Western countries. EBV infection and co‐infection of HPV/EBV were low in OPSCC. The prognosis of HPV‐positive OSPCC was more favorable.

This study attempted to research the molecular mechanism underlying the inhibitory role of miR-1225-5p in the malignant progression of glioblastoma. Bioinformatics analyses based on the gene expression omnibus (GEO) and Chinese glioma genome atlas (CGGA) databases showed that miR-1225-5p, as a favorable prognostic factor, was expressed at low levels in glioblastoma, and its expression was also related to WHO grade and age. The subsequent CCK-8 assay indicated that miR-1225-5p might prevent the malignant progression of glioblastoma, which was represented by that miR-1225-5p mimic reduced the viability of glioblastoma cells. Then, we predicted that FNDC3B might be a potential target gene of miR-1225-5p, and it was negatively correlated with the level of miR-1225-5p, which were confirmed by dual-luciferase reporter assay, qRT-PCR and western blot assays. Moreover, based on the analyses of the cancer genome atlas (TCGA), Oncomine and CGGA databases, FNDC3B was enriched in glioblastoma and high expression of FNDC3B led to poor prognosis. Finally, CCK8 and transwell experiments showed that the ability of miR-1225-5p to inhibit glioblastoma cell viability, invasion and migration was at least partially achieved by targeting FNDC3B. In general, these results revealed that the miR-1225-5p/FNDC3B axis contributes to inhibiting the malignant phenotype of glioblastoma cells, which lays a foundation for molecular diagnosis and treatment of glioblastoma.

OBJECTIVES Cardiovascular dysautonomia can be present at early, late and even prodromal stages of Parkinson's disease. This study aimed to describe the characteristics of 24-h ambulatory blood pressure (BP) monitoring and investigate the frequency of cardiovascular dysautonomia in Parkinson's disease without an abnormal BP history. METHODS Parkinson's disease patients without history of abnormal BP were consecutively enrolled from three Chinese centres, on whom office BP measurement, neurological evaluations and 24-h ambulatory BP monitoring were performed. RESULTS Totally, 101 Parkinson's disease patients (42.6% women) with an average age of 66.6 ± 8.2 years were included in our cohort, and data analysis revealed that 26 (25.74%) patients suffered from orthostatic hypotension, among whom 18 (69.23%) were symptomatic. Patients with orthostatic hypotension compared with those without had significantly higher nocturnal SBP level, and more severe nonmotor symptoms, autonomic dysfunction and cognitive impairment. Further, 54 out of 101 (53.47%) individuals had a reverse dipping pattern in SBP and/or DBP. Reverse dippers had more cases of orthostatic hypotension (P

Objective This study is conducted to investigate the effects differences of escitalopram with or without combined electroacupuncture (EA) among male inpatients with a diagnosis of alcohol dependence and comorbid protracted alcohol withdrawal symptoms (PAWS). Methods A total of 62 participants who met the inclusion criteria were enrolled in a two-arm randomized, placebo controlled, patients-blind trial and allocated to an escitalopram with real-EA group (real-EA group, patients= 31) and an escitalopram with sham-EA group (sham-EA group, patients= 31), respectively. In addition to the oral administration of escitalopram for total four weeks, patients in each group received corresponding EA treatment five days per week and two days off for consecutive four weeks. Both serum homocysteine (Hcy) test and electrophysiological tests, including event-related potentials (ERPs) and exploratory eye movement (EEM) were performed at pre- and post-treatment. Additionally, the global scores of Penn Alcohol Craving Scale (PACS), 17-items Hamilton Depression Rating Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used for assessing the subjective emotion experience of patients, respectively. Meanwhile, adverse effects were monitored and recorded. Results After four-week treatment, the global scores of PACS and HAMD-17 declined significantly in both groups (both P 0.05). According to the parameters of ERPs, significant declines for N2PL, P3PL, and P3amp were observed in both two groups (all P Conclusion (1) Escitalopram with EA may be a potential alternative therapy for mitigating PAWS among male inpatients with alcohol dependence. (2) Escitalopram with EA might improve the alcohol-dependence induced cognitive dysfunctions via upregulating the expression of Hcy.

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model (MCAO) and paired associated magnetic stimulation (PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments-the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the foot-fault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease caused by abnormal DNA replication of bone marrow stem cells and chemotherapy resistance is a major obstacle to the effective treatment of patients with CML. Imatinib (IM), a tyrosine kinase inhibitor (TKI), is a first-line drug clinically used for CML. Mounting evidence has indicated that the dysregulation of microRNAs (miRNAs) is associated with the chemoresistance of CML. In this study, miR-153-3p, which had been implicated with numerous types of tumors, was identified to be downregulated in IM-resistant CML cells. Upregulation of miR-153-3p significantly increased IM sensitivity and decreased the survival rate of IM-resistant CML cells, whereas downregulation of miR-153-3p attenuated these effects in IM-resistant CML cells. Upregulated miR-153-3p could decrease the autophagy caused by IM in IM-resistant CML cells. Dual-luciferase reporter assays confirmed that Bcl-2 is a direct target of miR-153-3p. Bcl-2 restoration reversed the increased sensitivity to IM induced by miR-153-3p-mimic transfection in IM-resistant CML cells. The results of the present study showed that dysregulated miR-153-3p may target Bcl-2 to promote the development of IM resistance and attenuate IM-induced apoptosis in CML. Therefore, miR-153-3p upregulation combined with IM treatment may serve as a promising therapeutic strategy for patients with low sensitivity.

Most recent semi-supervised deep learning (deep SSL) methods used a similar paradigm: use network predictions to update pseudo-labels and use pseudo-labels to update network parameters iteratively. However, they lack theoretical support and cannot explain why predictions are good candidates for pseudo-labels. In this paper, we propose a principled end-to-end framework named deep decipher (D2) for SSL. Within the D2 framework, we prove that pseudo-labels are related to network predictions by an exponential link function, which gives a theoretical support for using predictions as pseudo-labels. Furthermore, we demonstrate that updating pseudo-labels by network predictions will make them uncertain. To mitigate this problem, we propose a training strategy called repetitive reprediction (R2). Finally, the proposed R2-D2 method is tested on the large-scale ImageNet dataset and outperforms state-of-the-art methods by 5 percentage points., Accepted by AAAI 2020

The virtual restoration of cultural relics by adopting computer technology is the trend of cultural relics protection and value mining. In order to solve the problem of large error in the existing matching methods of non-thin-walled cultural relic fragments, in this paper, a matching method of cultural relic fragments is proposed, when the thickness feature and the contour feature are combined, and the strategy of coarse matching followed by fine matching is adopted. Firstly, the broken contour of cultural relic fragments is extracted, and the upper and lower contour lines are identified; secondly, the thickness feature is calculated and the thickness histogram is constructed. After that, the initial matching of fragments is completed according to the similarity of the histogram. Thirdly, the fracture contour is segmented, and the fragments of the mismatching relationship in the initial matching are also eliminated by the modified Hausdorff distance to optimize the coarse matching results. Finally, the SVD method is adopted to solve the rigid body transformation parameters, and the ICP algorithm is employed to accurately align the fine matching. The experimental results show that with the method in this paper, excellent matching results have been obtained regarding the fragments of the Terracotta Warriors. Compared with matching methods of other cultural relic fragments, the accuracy and algorithm cost of this method are better.

Aim: To analyze the impact of nongenetic factors and gene polymorphisms on warfarin dose requirements in elderly Shanghai Han Chinese patients. Materials & methods: Genotypes of CYP2C9 (rs1799853 and rs1057910), FPGS (rs7856096), ApoE (rs7412 and rs429358), GGCX (rs699664 and rs12714145), EPHX1 (rs4653436, rs1877724, rs1051740 and rs1131873), NQO1 (rs1800566 and rs10517), ABCB1 (rs1045642), VKORC1 (rs9923231) and CYP4F2 (rs2108622) in 214 patients with stable warfarin dose were determined and their demographic characteristics were recorded. Results: Multiple linear regression analysis revealed that VKORC1 rs9923231, CYP2C9*3 rs1057910, ApoE rs7412, age, BMI and concomitant amiodarone could explain 37.0% of the individual variations of daily stable warfarin dose. Conclusion: VKORC1 rs9923231, CYP2C9*3 rs1057910, ApoE rs7412, age, BMI and concomitant amiodarone play an important role in stable dose variation of warfarin in elderly Shanghai Han Chinese patients, whereas ABCB1 rs1045642 is not a significant genetic factor.

Macrophages are essential for wound repair after myocardial infarction (MI). CD226, a member of immunoglobulin superfamily, is expressed on inflammatory monocytes, however, the role of CD226 in infarct healing and the effect of CD226 on macrophage remain unknown. Methods: Wild type and CD226 knockout (CD226 KO) mice were subjected to permanent coronary ligation. CD226 expression, cardiac function and ventricular remodeling were evaluated. Profile of macrophages, myofibroblasts, angiogenesis and monocytes mobilization were determined. Results: CD226 expression increased in the infarcted heart, with a peak on day 7 after MI. CD226 KO attenuated infarct expansion and improved infarct healing after MI. CD226 deletion resulted in increased F4/80+ CD206+ M2 macrophages and diminished Mac-3+ iNOS+ M1 macrophages accumulation in the infarcted heart, as well as enrichment of α-smooth muscle actin positive myofibroblasts and Ki67+ CD31+ endothelial cells, leading to increased reparative collagen deposition and angiogenesis. Furthermore, CD226 deletion restrained inflammatory monocytes mobilization, as revealed by enhanced retention of Ly6Chi monocytes in the spleen associated with a decrease of Ly6Chi monocytes in the peripheral blood, whereas local proliferation of macrophage in the ischemic heart was not affected by CD226 deficiency. In vitro studies using bone marrow-derived macrophages showed that CD226 deletion potentiated M2 polarization and suppressed M1 polarization. Conclusion: CD226 expression is dramatically increased in the infarcted heart, and CD226 deletion improves post-infarction healing and cardiac function by favoring macrophage polarization towards reparative phenotype. Thus, inhibition of CD226 may represent a novel therapeutic approach to improve wound healing and cardiac function after MI.

BACKGROUND: To date, postoperative intractable cough (PIC) has not received adequate attention, and the complex perioperative factors when performing pulmonary resection often prevent researchers from addressing this issue. This study aimed to investigate the clinicopathological and radiographic indicators related to PIC in lung cancer patients. METHODS: In all, 112 patients who had had right upper lobectomy for primary lung cancer from January 2019 to December 2020 were retrospectively reviewed. We collected data via the electronic medical database of our department. Bronchial morphological features were investigated comprehensively via three-dimensional chest computer tomography reconstruction images. RESULTS: During outpatient follow-up visits, 41 (36.6%) patients complained about persistent dry cough after surgery. Compared with the non-cough group, patients in the refractory cough group showed significant differences in smoking history, right upper lobe stump length, changes of right bronchus intermedius (RBI) diameter, changes of right lower lobe (RLL) basal bronchus diameter, changes of RBI/RLL bronchial angle, and bronchial kink. However, according to multivariable regression analysis, stump length, bronchial kink, and diameter change of the right lower lobe basal bronchus were independently associated with postoperative refractory cough. A nebulization drug was prescribed for the 41 patients diagnosed with PIC, and 33 (80.5%) patients had improved by the next visit. CONCLUSIONS: After right upper lobectomy, the morphology of the remaining bronchial tree in the residual lung changed significantly. The bronchial morphological alterations were independent risk factors for PIC.

Objective Whether cervical disc arthroplasty (CDA) is superior to anterior cervical discectomy and fusion (ACDF) remains controversial, especially in relation to long‐term results. The present study aimed to evaluate the long‐term safety and efficiency of CDA and ACDF for cervical disc disease. Methods We performed this study according to the Cochrane methodology. An extensive search was undertaken in PubMed, Embase, and Cochrane databases up to 1 June 2019 using the following key words: “anterior cervical fusion,” “arthroplasty,” “replacement” and “artificial disc”. RevMan 5.3 (Cochrane, London, UK) was used to analyze data. Safety and efficiency outcome measures included the success rate, functional outcome measures, adverse events (AE), adjacent segment degeneration (ASD), secondary surgery, and patients’ satisfaction and recommendation rates. The OR and MD with 95% confidence interval (CI) were used to evaluate discontinuous and continuous variables, respectively. The statistically significant level was set at P

The commonly used left atrial appendage (LAA) occlusion (LAAO) devices, Watchman (Boston Scientific, Marlborough, MA, USA) and Amulet (Abbott, Plymouth, Minnesota, USA), both rely on oversizing for stabilization. Therefore, occluding large LAA (ostium g=31mm for Watchman or landing zone g=31mm for Amulet) are not possible. LAmbre (Lifetech Scientific Co., Shenzhen, China) device has an additional stabilization mechanism by catching the LAA trabeculations using its 8 claws1. This potentially allows LAmbre in occluding large LAA with ostium up to 40mm, i.e. size of its largest cover. The study aimed to evaluate procedural and short-term outcomes of LAmbre device in occluding large LAA.

Background Ancestry estimation of skulls is under a wide range of applications in forensic science, anthropology, and facial reconstruction. This study aims to avoid defects in traditional skull ancestry estimation methods, such as time-consuming and labor-intensive manual calibration of feature points, and subjective results. Results This paper uses the skull depth image as input, based on AlexNet, introduces the Wide module and SE-block to improve the network, designs and proposes ANINet, and realizes the ancestry classification. Such a unified model architecture of ANINet overcomes the subjectivity of manually calibrating feature points, of which the accuracy and efficiency are improved. We use depth projection to obtain the local depth image and the global depth image of the skull, take the skull depth image as the object, use global, local, and local + global methods respectively to experiment on the 95 cases of Han skull and 110 cases of Uyghur skull data sets, and perform cross-validation. The experimental results show that the accuracies of the three methods for skull ancestry estimation reached 98.21%, 98.04% and 99.03%, respectively. Compared with the classic networks AlexNet, Vgg-16, GoogLenet, ResNet-50, DenseNet-121, and SqueezeNet, the network proposed in this paper has the advantages of high accuracy and small parameters; compared with state-of-the-art methods, the method in this paper has a higher learning rate and better ability to estimate. Conclusions In summary, skull depth images have an excellent performance in estimation, and ANINet is an effective approach for skull ancestry estimation.

ObjectiveTo investigate the association between hypothyroxinemia and the risk of preeclampsia–eclampsia and gestational hypertension.DesignHistorical cohort study.MethodsThe study included pregnant individuals who delivered live-born singletons and had at least one thyroid function assessment during pregnancy at a tertiary hospital. Hypothyroxinemia was defined as thyroid-stimulating hormone (TSH) levels within the normal reference range and free thyroxine (FT4) levels lower than the tenth percentile. Risk ratios (RRs) with 95% confidence intervals (95% CIs) for preeclampsia–eclampsia and gestational hypertension between women with and without a diagnosis of hypothyroxinemia during pregnancy were estimated using a generalized estimating equation model.ResultsA total of 59,463 women with live-born singletons were included in the analysis. Logistic regression models with restricted cubic spline suggested that there was a U-shaped association between FT4 levels and preeclampsia–eclampsia risk. Compared with euthyroid women, those with hypothyroxinemia had an increased risk of preeclampsia–eclampsia (RR = 1.16, 95% CI: 1.02–1.31), and the risk increased with the increasing severity of hypothyroxinemia (p for trend < 0.001). Moreover, persistent hypothyroxinemia from the first to second trimesters was associated with an increased risk of preeclampsia–eclampsia (RR = 1.37, 95% CI: 1.03–1.83), especially for women with severe hypothyroxinemia (RR = 1.70, 95% CI: 1.12–2.58). In contrast, there was no association between hypothyroxinemia and gestational hypertension.ConclusionOur study suggested that hypothyroxinemia was only associated with an increased risk of preeclampsia–eclampsia, especially in women with persistent hypothyroxinemia in the first half of pregnancy. Analyses of the associated risk of gestational hypertension with hypothyroxinemia were not significant.

Inflammation and disease are closely related. Inflammation can induce various diseases, and diseases can promote inflammatory response, and two possibly induces each other in a bidirectional loop. Inflammation is usually treated using synthetic anti-inflammatory drugs which are associated with several adverse effects hence are not safe for long-term use. Therefore, there is need for anti-inflammatory drugs which are not only effective but also safe. Several researchers have devoted to the research and development of effective anti-inflammatory drugs with little or no side effects. In this review, we studied some small molecules with reported anti-inflammatory activities and hence potential sources of anti-inflammatory agents. The information was retrieved from relevant studies published between January 2019 and May, 2021 for review. This review study was aimed to provide relevant information towards the design and development of effective and safe anti-inflammation agents.

Central nervous system (CNS) lesions are major causes of human death and disability worldwide, and they cause different extents of motor and sensory dysfunction in patients. Thus, it is crucial to develop new effective neuroprotective drugs and approaches targeted to the heterogeneous nature of CNS injury and disease. L-serine is an indispensable neurotrophic factor and a precursor for neurotransmitters. Although L-serine is a native amino acid supplement, its metabolic products have been shown to be essential not only for cell proliferation but also for neuronal development and specific functions in the brain. Growing evidence has suggested that L-serine regulates the release of several cytokines in the brain under some neuropathological conditions to recover cognitive function, improve cerebral blood flow, inhibit inflammation, promote remyelination and exert other neuroprotective effects on neurological injury. L-serine has also been used to treat epilepsy, schizophrenia, psychosis, and Alzheimer’s Disease as well as other neurological diseases. Furthermore, the dosing of animals with L-serine and human clinical trials investigating the therapeutic effects of L-serine generally support the safety of L-serine. The high significance of this review lies in its emphasis on the therapeutic potential of using L-serine as a general treatment for numerous CNS diseases and injuries. Because L-serine performs a broad spectrum of functions, it may be clinically used as an effective neuroprotective agent.

Knowledge distillation (KD) is a popular method to train efficient networks ("student") with the help of high-capacity networks ("teacher"). Traditional methods use the teacher's soft logits as extra supervision to train the student network. In this paper, we argue that it is more advantageous to make the student mimic the teacher's features in the penultimate layer. Not only the student can directly learn more effective information from the teacher feature, feature mimicking can also be applied for teachers trained without a softmax layer. Experiments show that it can achieve higher accuracy than traditional KD. To further facilitate feature mimicking, we decompose a feature vector into the magnitude and the direction. We argue that the teacher should give more freedom to the student feature's magnitude, and let the student pay more attention on mimicking the feature direction. To meet this requirement, we propose a loss term based on locality-sensitive hashing (LSH). With the help of this new loss, our method indeed mimics feature directions more accurately, relaxes constraints on feature magnitudes, and achieves state-of-the-art distillation accuracy. We provide theoretical analyses of how LSH facilitates feature direction mimicking, and further extend feature mimicking to multi-label recognition and object detection., Comment: To appear in IEEE Trans. PAMI

Recent preclinical studies have reported that pretreatment with the novel and highly-selective dopamine D(3) receptor (D(3)R) antagonists R-VK4–40 or VK4–116 attenuates the abuse-related behavioral effects of oxycodone while enhancing its analgesic properties. However, whether these observed effects are generalizable to the broad class of D(3)R antagonists and/or extend to opioids other than oxycodone has not been extensively explored. The present study sought to assess the impact of pretreatment with another selective D(3)R antagonist, PG01037, on several behavioral effects of morphine in mice. C57Bl/6J mice were pretreated with PG01037 (0 – 10 mg/kg) and tested for 1) hyperlocomotion induced by acute morphine (5.6 – 56 mg/kg), 2) locomotor sensitization following repeated morphine (56 mg/kg), 3) antinociception following acute morphine (18 mg/kg), and 4) catalepsy following administration of PG01037 alone or in combination with morphine (56 mg/kg). PG01037 dose-dependently attenuated morphine-induced hyperlocomotion and morphine-induced antinociception at doses that did not alter basal locomotion or nociception alone, but did not prevent the induction of locomotor sensitization following repeated morphine administration. Moreover, PG01037 did not induce catalepsy either alone or in combination with morphine. These results suggest that attenuation of acute opioid-induced hyperactivity may be a behavioral effect shared among D(3)R-selective antagonists, thus supporting continued investigations into their use as potential treatments for opioid use disorder. However, PG01037 is unlike newer, highly-selective D(3)R antagonists in its capacity to reduce opioid-induced antinociception, indicating that modulation of opioid analgesia may vary across different D(3)R antagonists.