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The combined use of gastrointestinal hormones for treating metabolic diseases is gaining increasing attention. The potential of developing novel dual agonists targeting both cholecystokinin 1 (CCK-1) receptor and glucagon-like peptide 1 (GLP-1) receptor to improve the treatment of type 2 diabetes and obesity have not been fully explored. In this investigation, we reported a series of novel GLP-1/CCK-1 receptor co-agonists constructed by linking the C-terminus of a GLP-1 receptor agonist (bullfrog GLP-1) to the N-terminus of a CCK-1 receptor selective agonist NN9056. In comprehensive in vitro assays, these co-agonists exhibited complete agonistic potency on GLP-1 and CCK-1 receptor. Remarkably, 1f displayed superior hypoglycemic and insulinotropic effects when compared to NN9056 and semaglutide. Evaluation in Kunming and diet-induced obesity (DIO) mice unveiled significant acute and enduring hypoglycemic effects of 1f. Administration of 1f to DIO mice resulted in substantial weight loss, normalized lipid metabolism, and enhanced glucose regulation. These preclinical observations strongly advocate for the therapeutic potential CCK-1 and GLP-1 pathways could be harnessed in a single fusion peptide, yielding a promising combination therapy strategy for treating metabolic disorders.

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The increasing prevalence of the aging population, and inadequate and uneven distribution of medical resources, have led to a growing demand for telemedicine services. Gait disturbance is a primary symptom of neurological disorders such as Parkinson's disease (PD). This study proposed a novel approach for the quantitative assessment and analysis of gait disturbance from two-dimensional (2D) videos captured using smartphones. The approach used a convolutional pose machine to extract human body joints and a gait phase segmentation algorithm based on node motion characteristics to identify the gait phase. Moreover, it extracted features of the upper and lower limbs. A height ratio-based spatial feature extraction method was proposed that effectively captures spatial information. The proposed method underwent validation via error analysis, correction compensation, and accuracy verification using the motion capture system. Specifically, the proposed method achieved an extracted step length error of less than 3 cm. The proposed method underwent clinical validation, recruiting 64 patients with Parkinson's disease and 46 healthy controls of the same age group. Various gait indicators were statistically analyzed using three classic classification methods, with the random forest method achieving a classification accuracy of 91%. This method provides an objective, convenient, and intelligent solution for telemedicine focused on movement disorders in neurological diseases.

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Retrospective analysis.To report a child with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome admitted to the Department of Pediatric Nephrology and Rheumatology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University in March 2020.A 14-year-old boy presented to hospital due to acne for more than 2 months, fever for more than 50 days, and hip pain for 2 weeks.The patient was diagnosed and treated as acne combined with infection and arthritis in other hospitals for more than 2 months without remission.He was initially diagnosed as juvenile idiopathic arthritis, acne combined with infection on admission.The disease was aggravated even after medications of anti-infection and anti-inflammatory drugs.After multidisciplinary consultation, the patient was diagnosed as SAPHO syndrome.The patient recovered from medications of Celecoxib, Sulfasalazine, recombinant human tumor necrosis factor receptorⅡ: IgG Fc fusion protein and other drugs.SAPHO syndrome is rare, especially in children, which is easily misdiagnosed.This case report suggested that SAPHO should be considered in children with acne, especially those combined with arthritis.

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The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic.

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@# Objective To explore the effects of transcutaneous electrical acupoint stimulation (TEAS) on upper limbs function in chronic stroke patients. Methods From March, 2016 to May, 2018, 53 patients were randomly divided into control group (n = 27) and research group (n = 26). All the patients received conventional rehabilitation, and the research group received additional intervention of TEAS, for six weeks. They were assessed with Manual Muscle Test (MMT) on upper limbs, modified Ashworth Scale (MAS), Fugl-Meyer Assessment-upper extremities (FMA-UE), Hand Motor Status Scale and modified Barthel Index (MBI) before, at the end of 6-week treatment and twelve weeks after treatment. Results There was no significant difference in all the scores between two groups at the end of 6-week treatment (t < 1.511, P > 0.05). The scores of MMT of wrist dorsal extension, FMA-UE and MBI were better in the research group than in the control group twelve weeks after end of treatment (t > 2.312, P < 0.05). Conclusion TEAS may promote the recovery of hands and upper limbs function in chronic stroke patients.

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In recent years, a large number of studies have achieved tumor targeting by mesenchymal stem cells (MSC)-based delivery system attributed to the tumor tropism of MSCs. Biomacromolecules and antineoplastic drugs loaded on MSC via internalization or cell membrane anchoring can be released or expressed at tumor site to perform their antitumor effects. The genetically modified MSC are extensively studied, however, the applications of MSCs in targeted delivery of antineoplastic drug with small molecules are not well summarized. In this review, MSCs homing mechanism and the distribution of injected MSCs is introduced; the examples of antitumor drug-primed MSCs and drug loaded MSCs are presented; the drug loading and releasing process from MSCs is also illustrated; finally, challenges and future perspectives of MSCs-based drug delivery system on realizing its full potential are prospected.

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Enteric nervous system abnormalities are the main cause of severe chronic constipation in children.These abnormalities are collectively known as intestinal dysganglionosis,including Hirschsprung's disease (HD),and Hirschsprung's disease allied disorders(HAD) such as immature ganglion,hypoganglionosis(HG) and intestinal neuronal dysplasia(IND).HD and HAD have similar clinical manifestations,and accurate diagnosis is challenging.In this paper,difficulties in diagnosis and treatment of HAD are introduced.

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<p><b>OBJECTIVE</b>To prepare freeze-dried long-circulation oridonin liposomes with optimized parameters.</p><p><b>METHODS</b>Ethanol injection method followed by freeze-drying was used to prepare the liposomes. Sephadex column was used to purify liposomes. Effects of formulation factors on entrapment efficiency of long-circulation oridonin liposomes were studied. The particle size, distribution and in vitro release were determined. Pharmacokinetics of oridonin liposomes in rats was determined by HPLC and the pharmacokinetic parameters calculated by Kinetica(TM) software were compared with conventional oridonin liposomes and solution.</p><p><b>RESULTS</b>The optimized lipid formulation for long-circulation liposomes was composed of soy lecithin, cholesterol and DSPE-PEG 2000 with a ratio of 1:0.5:1.8(w/w). The ratio of drug to lipid was 1:6. Freeze-drying protectant was a mixture of glucose and mannitol (3:1). The entrapment efficiency (EE) of long-circulation oridonin liposomes was about 65%. The particle size of liposomes after hydrolyzation was 164 nm with good DPI. The liposomes showed a sustained drug release in vitro. Intravenous injected oridonin fitted with two-compartment pharmacokinetic model. The MRT of long-circulation liposomes was 2 times and 6 times and AUC was about 2 times and 3 times of conventional liposomes and oridonin solution, respectively.</p><p><b>CONCLUSION</b>Freeze-dried liposomes with high EE have been obtained by the proposed approach. This long-circulation liposomes extend oridonin half time and significantly increase AUC in rats.</p>

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<p><b>OBJECTIVE</b>To summarize the experience of heart-shaped anastomosis operation in patients with Hirschsprung's disease.</p><p><b>METHODS</b>Hirschsprung's disease treated by heart-shaped anastomosis, improvement of surgery procedure, and complications were reviewed retrospectively.</p><p><b>RESULTS</b>Of 193 cases, 152 completed follow-up. Early complications included urine retention (2 cases), enteritis (10), anastomosis stricture (1), and intestinal obstruction (2). Late complications (22 cases) included adhesive intestinal obstruction (2), constipation (5), incision hernia (2), enteritis (6), and occasionally stool stains (7). Neither infection in celiac, pelvic cavity and wound nor incontinence or death occurred in all patients.</p><p><b>CONCLUSION</b>Heart-shaped anastomosis procedure can effectively reduce the complications ceased by Hirschsprung's disease operation and is superior to other procedures.</p>

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