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 explore the expression level of PPFIA4 in hepatocellular carcinoma tissues and HCCLM3 cells and its regulation of the biological behavior of hepatocellular carcinoma. Methods : Bioinformatics analysis, Western blot, and immunohistochemistry were employed to detect the expression of PPFIA4 in tumor tissues of patients with hepatocellular carcinoma and analyze the prognosis of these patients. An siRNA plasmid was designed to knock down the expression of PPFIA4 in HCCLM3 cells. The effects of PPFIA4 knockdown on the migration and invasion abilities of HCCLM3 cells were then evaluated using scratch healing and Transwell assays. Furthermore, Western blot was utilized to detect the expression levels of epithelial-mesenchymal transition(EMT)-related protein markers in the HCCLM3 cell line after transfection with the siRNA plasmid. Results: PPFIA4 was highly expressed in hepatocellular carcinoma tissues and hepatocellular carcinoma cells( HCCLM3, Li-7, MHCC97H); the high expression of PPFIA4 indicated that the clinical stage of patients was late and the overall survival(OS) was short. After knocking down the expression of PPFIA4 in HCCLM3 cell line, the migration and invasion ability of HCCLM3 cells decreased(P<0.001) and the expression of EMT markers changed. The expression of epithelial cell marker E-cadherin increased(P<0.01), while the expression of mesenchymal markers Vimentin and N-cadherin decreased(P<0.05,P<0.01). Conclusion PPFIA4 is highly expressed in hepatocellular carcinoma tissues and hepatocellular carcinoma cell lines and is associated with poor prognosis of patients. Silencing PPFIA4 can regulate the biological behavior of hepatocellular carcinoma cells and inhibit the migration and invasion of HCCLM3 cells. The specific mechanism may be related to EMT.

Objective: To estimate the epidemic threshold and graded intensity thresholds of influenza in Zhejiang Province from 2012 to 2023 using the moving epidemic method (MEM), and evaluate the intensity of influenza epidemics, so as to provide the reference for influenza prevention and control in Zhejiang Province. Methods: The positive rates of influenza virus per week during the influenza epidemic seasons (from 40th week to 20th week of the following year) in Zhejiang Province from 2012 to 2022 were collected through the Chinese Influenza Surveillance Information System. A MEM model was established and optimized using cross-validation. The maximum accumulated rates percentage was used to divide the epidemic into pre-epidemic, epidemic, and post-epidemic periods, and to estimate the epidemic thresholds and graded intensity thresholds. The intensity of influenza epidemics in Zhejiang Province during the 2022-2023 epidemic season were assessed. Results: The positive rates of influenza virus in five epidemic seasons from 2012 to 2022 were included in the model. The MEM model performed best when the parameter δ was set to 1.5, with a sensitivity of 0.971, a specificity of 0.745, and a Youden's index of 0.716. According to the model analysis, the epidemic beginning and ending thresholds of influenza in Zhejiang Province during the 2022-2023 epidemic season were 19.32% and 10.92%, respectively, and the medium, high, and extremely high intensity thresholds were 48.65%, 63.49%, and 68.47%, respectively. During 2022-2023, the influenza epidemic was in the pre-epidemic period from the 40th week in 2022 to the 7th week in 2023; the epidemic period was from the 8th to the 18th week, the epidemic intensity was low in the 8th week and increased to a high level in the 9th week, and reached to a extremely high level from the 10th to the 13th week, then fell to the high and the medium level in the 14th week and 15th week, respectively, and fell to a low level from the 16th to the 18th week; the influenza epidemic entered the post-epidemic period since the 19th week. Conclusion MEM could be applied for evaluation of influenza epidemic intensity, providing the reference for early identification and taking graded preventive and control measures.

Objective To explore the research status and trends in the field of post-stroke foot drop. Methods The literature on post-stroke foot drop was retrieved from the Web of Science Core Collection database from inception to January,2024.The data were analyzed using VOSviewer and CiteSpace. Results A total of 490 articles were included.The annul articles were published more and more year by year since 1992,peaking in 2020.The main institutions were located in USA.The literature focused on the fields of medicine,healthcare and clinical studies.There were as many as 230 papers on rehabilitation.The most frequency key-words were rehabilitation,hemiplegic gait,electrical stimulation,foot drop,and stroke,and so on.Keyword co-occurrence analysis showed ten major clusters as motor rehabilitation,neurorehabilitation technology,gait analy-sis,functional recovery technology,and assessment of rehabilitation treatment effects,and so on. Conclusion Researches on the rehabilitation of post-stroke foot drop are moving towards the integration of technology and therapeutic methods,emphasizing the assessment of motor function and evidence of treatment effects,and exploring personalized rehabilitation plans.

BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

The stability of marginal bone level is an important factor in ensuring long-term good clinical efficacy of implantation.The design of implant-abutment interface(IAI)is of considerable importance,including whether undergoing multiple abutment disconnection,whether platform switching is used,connection type,connection torque,and connection material differences.These fac-tors can affect the micro gap and micro movement of the connection interface,which change the size of micro leakage and mechanical stability,thereby affecting the long-term clinical efficacy of implants.This article presents a detailed review of the progress of research on different designs in implant-abutment interface,in order to provide a theoretical basis for the selection and operation of abutments in clinical diagnosis and treatment.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Sleep is an important activity of daily life for individuals,and sleep disorders can seriously affect their physical and mental health.This article summarizes the impact of vestibular stimulation on sleep,and reviews feasible and effective intervention methods from swing movement,galvanic vestibular stimulation,and weighted blankets stimulation,in order to provide new ideas and methods for the diagnosis and treatment of sleep disorders.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.