Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Humans ; Asthma/drug therapy* ; Biological Therapy

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Facial Paralysis/etiology* ; Diagnosis, Differential ; Jugular Foramina ; Retrospective Studies ; Cough ; Hoarseness ; Neoplasm Recurrence, Local ; Chondrosarcoma/surgery*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective To explore the influence of WeChat platform rehabilitation guidance mode on refracture of osteoporotic fracture patients.Methods Totally 100 osteoporotic fracture patients admitted to the Department of Orthopedics of the hospital from 2018 to 2019 were selected and randomly divided into control group and experimental group with 50 patients in each group.The control group adopted the conventional discharge rehabilitation guidance mode,and the experimental group implemented WeChat platform rehabilitation guidance mode on this basis,including WeChat platform construction and detailed intervention mode.The changes of bone mineral density and the recurrence rate of osteoporotic fracture were compared between the two groups at admission and after 3 years of follow-up.Results There were 7 cases of lost follow-up in the experimental group,and there were 6 cases of lost follow-up in the control group.After 3 years,the bone mineral density of the experimental group was significantly higher than that of the control group,and the recurrence fracture rate was significantly lower than that of the control group(P<0.05).Conclusion The application of WeChat platform rehabilitation guidance mode can effectively improve bone density and reduce the incidence of refracture in osteoporotic fracture patients.

OBJECTIVE: To compare clinical effects of the improved interface screw fixation of femoral end of anterior cruciate ligament with classic femoral lateral loop plate fixation. METHODS: A retrospective analysis of 65 patients who underwent arthroscopic anterior cruciate ligament reconstruction from January 2019 to September 2021 were performed. According to the different fixation methods of the femoral side, 35 patients were divided into loop plate fixation(loop plate group), including 27 males and 8 females, aged from 18 to 50 years old with an average of (35.00±7.60) years old;30 patients in interface screw fixation(interface screw group), including 20 males and 10 females, aged from 18 to 50 years old with an average of (32.00±8.50) years old. Hospital stay, hospital expenses, operation time, complications, C-reactive protein at 1, 3, 6 days after operation, and postoperative Lysholm score and International Knee Documentation Committee(IKDC) score at 18 months were compared between two groups. RESULTS: All patients were successfully operated, and obtained follow-up from 18 to 36 months with an average of (25.16±4.50) months. Anterior drawer test and Lachman test of all patients turned to negative. There were no statistical differences in hospital stay, hospital expenses and complications between two groups(P>0.05);operation time in loop plate group was (74.00±6.84) min, and (91.67±6.34) min in interface screw group, and had difference between two groups(P<0.05). C-reactive protein on the 1st and 3rd day after operation was (40.00±10.10), (20.00±8.23) mg·L^-1 in loop plate group, and (60.00±8.93), (30.00±8.66) mg·L^-1 in interface nail group, had statistical difference between two groups (P<0.05);while there was no difference in C-reactive protein on the 6th day after operation(P>0.05). At 18 months after operation, Lysholm and IKDC scores showed no significant difference between two groups (P>0.05). In loop plate group, medullary enlargement on coronal and sagittal views were (2.75±0.19) mm, (1.55±0.25) mm, and (2.81±0.22) mm, (1.61±0.20) mm in interface screw group, and had statistical difference between two groups(P<0.05). CONCLUSION In the reconstruction of anterior cruciate ligament, the common interface screw on the femoral side is changed to the sheath interface screw, and intramedullary screw is changed to the compression and fixation of tendon from outside to inside of joint. Although the operation procedure is relatively complicated and operation time is slightly longer, it has advantages of no residual metal foreign body after operation, and clinical effect is no different from classical loop plate suspension fixation, which is still a good choice.
Female ; Male ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; C-Reactive Protein ; Retrospective Studies ; Femur ; Anterior Cruciate Ligament Reconstruction ; Bone Screws

Objective:To investigate the effect of curcumin on renal fibrosis in lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) in adult SD rats.Methods:Twenty-four male SD rats were randomly (random number) divided into four groups: control group, ARDS group, low dose group, and high dose group ( n=6 per group). In the control group, the rats were given atomization intratracheal of standard saline 2 mL/kg; in the ARDS group, low-dose group, and high-dose group, the rats were given atomization intratracheal of 4 mg/kg LPS; in the low-dose group, the rats were given curcumin 100 mg/d by the oral administration, and in the high-dose group, the rats were given curcumin or 200 mg/d respectively. After seven days, the rats were sacrificed. The superoxide dismutase (SOD) activity and the content of malondialdehyde (MDA) and glutathione (GSH) in renal tissue were detected by colorimetric assay. Nuclear factor kappa-B p65 (NF-κB p65) and transforming growth factor-β1 (TGF-β1) were detected by Western blot. The expression of interleukin-6 (IL-6) mRNA, proline hydroxylase 3 (PHD3) mRNA, vascular endothelial growth factor (VEGF) mRNA and erythropoietin receptor (EPOR) mRNA were detected by quantitative real-time PCR (qRT-PCR). HE staining and Masson staining were used to assess pathological damage. One-way analysis of variance was used for comparison among multiple groups and SNK method was used for comparison between two groups. Results:Compared with the control group, the SOD activity and GSH content in the ARDS group, low-dose group, and high-dose group were significantly decreased (all P<0.05); the protein expression levels of MDA, NF-κB p65, and TGF-β1 were increased significantly, and IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were significantly upregulated (all P<0.05). HE staining showed inflammatory cell infiltration, and fibrogenesis in kidney tissue, and Masson staining showed deposition of collangen-like substance. Compared with the ARDS group, SOD activity and GSH content were increased, while the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the low-dose group and high-dose group (all P<0.05). Curcumin therapy reduced inflammatory cellular infiltration, and the deposition of collagen-like substance in kidney tissue. Compared with the low-dose group, SOD activity and GSH content were increased in the high-dose group (all P<0.05), and the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the high-dose group (all P<0.05). The high-dose group exhibited a significant reduction in edema, and a decrease of the deposition of collagen-like substance in kidney tissue. Conclusions:Curcumin can inhibit the development of renal fibrosis induced by acute respiratory distress syndrome in rats, and its mechanism may be related to inhibiting the expression of inflammatory factors and enhancing hypoxia tolerance.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.