ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

Objective To construct a canine model of vocal cord scar by low-termperature plasma ablation and screen the target genes closely related to the formation of vocal cord scar.Methods Four Chinese rural canines were treated with plasma ablation under the support of laryngoscope and endoscope,and the left vocal cords were injured to the muscle layer.The contralateral sides were left untreated.The gross morphology of vocal cord was observed before operation,immediately after operation,3 weeks after operation and 12 weeks after operation.The pathologi-cal structure of vocal cords was observed by HE stainning,and the ultrastructure of vocal cords was observed by transmission electron microscopy.In addition,high-throughput sequencing was used to analyze the differences in gene expression between the bilateral vocal cords,and the target genes with significantly different expression were screened out.Results In general morphology,the normal vocal cords were banded and well closed.At 3 weeks af-ter operation,the vocal cords were congested and swollen,with uneven edges and red granulation tissues were seen.At 12 weeks after operation,the vocal cord wound was localized contracture and depression,and scar was formed.HE staining showed obvious thickening of the squamous epithelium of the scarred vocal cords,thickening and disor-dered arrangement of the fiber layer,local clumping or bundle aggregation,and scattered fiber bundles were also seen in the muscle layer.Transmission electron microscopy showed interstitial thickening,uneven density,cell swelling,unclear intercellular boundary,proliferation of nuclei and mitochondria,and cells in an active state.High-throughput sequencing analysis revealed that many gene families were involved in the process of vocal cord scar re-pair,including IL family,CCL and CXCL family,MMPs family and its inhibitor TIMPs family,Wnt family,HSP family,MAPK family and TGF-β family.Conclusion We successfully constructed the canine model of vocal cord scar by low-temperature plasma ablation and screened out the target genes closely related to the formation of vocal cord scar by high-throughput sequencing,which provides certain reference value for exploring the mechanism of vo-cal cord scar.

Objective To investigate the effect of ERK inhibitor PD98059 on the proliferation and differentia-tion of rat otocyst osteoblasts.Methods SD neonatal rat osteoblasts were extracted by two-step digestion with 0.25％pancreatin and type Ⅰ collagenase,and co-cultured with ERK inhibitor PD98059 at concentrations of 0 μmol/L,10 μmol/L,25 μmol/L and 50 μmol/L,respectively.Then,the osteoblasts proliferation of the four groups were assessed by EDU method for 4 consecutive days.The proliferation trend of each group was compared and analyzed.Osteoblasts were differentiated by β-sodium glycerophosphate,L-vitamin C and dexamethasone at concentrations of 10 mmol/L,50 ug/ml and 10-7 mol/L.After 24 h,the mRNA expression levels of osteogenic fac-tors which include Ocn,Bsp,Runx2,Bmp2,OPG and RANKL in each group were detected by RT-qPCR,and the differences of the results were analyzed.Results All the concentrations of ERK inhibitor PD98059 could inhibit the proliferation of osteoblasts in SD neonatal rat,and the inhibitory effect of PD98059 at concentrations of 10 μmol/L was significantly greater than that of the other three groups(P＜0.05).In addition,all the concentrations of PD98059 could inhibit the expressions of Ocn,Bsp,Runx2,Bmp2 and OPG mRNA.The mRNA expressions of Ocn,Bsp,Runx2 and Bmp2 in 10 μmol/L PD98059 group were significantly lower than those in 0 μmol/L,25μmol/L and 50 μmol/L PD98059 groups(P＜0.05).The mRNA expressions of OPG in 10 and 25 μmol/L PD98059 groups were significantly lower than those in 0 and 50 μmol/L PD98059 groups(P＜0.05),and there was no significant difference between the first two groups(P＞0.05).The CT value of RANKL mRNA was not detec-ted in all groups.Conclusion ERK pathway inhibitor PD98059 can both inhibit the proliferation and differentiation of osteoblasts in rat otocyst.Therefore,we speculate that ERK1/2-MAPK pathway may mediate the formation of tympanosclerosis by affecting the proliferation and differentiation of rat otocyst osteoblasts.

Malaria is an insect-borne disease transmitted by Anopheles mosquitoes or the importation of Plasmodium-infected blood, posing a serious threat to human health and life safety. This study aims to analyze the incidence of malaria in Qingdao at various stages from 1949 to 2021, to collate the control measures taken at different epidemic stages to assess the effectiveness of malaria control, and to identify a set of malaria control strategies suitable for Qingdao, while providing Chinese experience for other countries or cities in their malaria elimination efforts. A retrospective survey was used to collect information on malaria cases, control measures and prevention and control effects in Qingdao from 1949 to 2021, and to evaluate malaria control strategies and measures in Qingdao. 704 155 cases have been reported from 1949 to 2021, with three epidemic peaks: the incidence rate was 1715.9/100 000 in 1961, 1409.7/100 000 in 1965, and the most severe case occurred in 1972, with an incidence rate of 1635.6/100 000 and a case count exceeding 90 000. Throughout the various stages of malaria epidemics, Qingdao has effectively eliminated indigenous malaria by implementing diverse preventive and control measures. Since the last indigenous case of Plasmodium vivax was reported in 2002, all locally reported cases have been imported, mainly by returning migrant workers from Africa. This study examines a range of malaria prevention and control strategies and interventions that are appropriate for Qingdao. These measures have enabled Qingdao to successfully eliminate malaria and maintain malaria-free status for more than 20 years. These measures can also serve as a reference for similarly situated cities in Africa and Southeast Asia.

Objective To evaluate the safety,tolerability and pharmacokinetic profiles of naldemedine in Chinese healthy adult subjects after single and multiple administrations.Methods After single and multiple oral administrations of naldemedine to 10 healthy Chinese subjects,the plasma concentrations of naldemedine and its metabolite(nor-naldemedine)were measured by liquid chromatography-mass spectrometry,and the pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.3.1 software.Results Compared with single administration,naldemedine showed no significant change in the tmax(1.06 h for single and 1.08 h for multiple)and Cmax(4.16 ng·mL-1 for single and 4.11 ng·mL-1 for multiple),higher AUC0-τ than that of single(23.88 ng·h·mL-1 for single and 28.93 ng·h·mL-1 for multiple),slightly prolonged t1/2(9.26 h for single,12.50 h for multiple),there was a slight drug accumulation after multiple doses(accumulation ratio of 0.99 for Cmax and 1.22 for AUC);t1/2(18.10 h for single,29.30 h for multiple),Cmax(0.19 ng·mL-1 for single,0.38 ng·mL-1 for multiple),and AUC0-τ(3.13 ng·h·mL-1 for single,6.02 ng·h·mL-1 for multiple)were all significantly elevated with nor-naldemedine,and the tmax(single was 3.49 h and multiple was 3.56 h)did not change significantly.The Cmax ratio and AUC ratio of metabolites to naldemedine were significantly elevated,and accumulation was present after multiple administrations(accumulation ratio of 2.01 for Cmax and 1.95 for AUC).All adverse events that occurred after treatment were mild.Conclusion After multiple oral administrations of 0.2 mg naldemedine tablets to Chinese healthy subjects(single dose on day 1 and once daily on days 4-13),the drug was eliminated rapidly with mild accumulation,and reached a steady state before the second dose of the multiple-dosing phase,and the product has a favorable safety and tolerability profiles.

Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.

Objective To evaluate the methylation levels of DNA at six specific CpG sites located in the mRNA region of histone cluster 4 subfamily F member 6(HIST1H4F)gene and determine their diagnostic signifi-cance about lung cancer.Methods The DNA methylation levels of 15 cases of lung cancer and adjacent paired nor-mal lung tissue were detected using pyrophosphate sequencing.Based on preliminary evaluation,a methylation-sensitive restriction enzyme-fluorescence quantitative PCR(MSRE-qPCR)method was developed to detect DNA methylation levels in the test group(60 cases of lung adenocarcinoma,38 cases of squamous cell carcinoma,30 cases of benign diseases,and 26 cases of normal lung tissue)and the validation group(36 cases of lung adenocarci-noma,16 cases of squamous cell carcinoma,21 cases of benign diseases,and 23 cases of normal lung tissue).The diagnostic value was evaluated using ROC curves.Results The results of pyrophosphate sequencing showed that the methylation levels of lung cancer were significantly higher than that of paired normal lung tissue(P<0.005).The detection results of MSRE-qPCR showed that the areas under the ROC curve for diagnosing lung cancer in the test group and validation group were 0.894 and 0.888,with sensitivity of 76.5%and 73.1%,and specificity of 92.9%and 97.7%,respectively.The methylation levels were significantly positively correlated with smoking in lung cancer patients(r=0.273,P<0.01).Conclusion The six CpG sites in the mRNA region of the HIST1H4F gene can serve as biomarkers for diagnosing lung cancer,providinga new molecular target for clinical lung cancer diagnosis.

Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?

Objective To study the medication law of Professor Qian Ying in the treatment of primary liver cancer based on data mining technology;To provide ideas for the clinical treatment of primary liver cancer.Methods Outpatient TCM prescriptions of Professor Qian Ying for the treatment of liver cancer from November 2008 to August 2020 were collected,and a data table was established after sorting.The drug frequency,property and taste and tropism were analyzed using Excel 2019.The medical case analysis module of the Great Physician Inheritance Platform was used to analyze the core drugs,the symbiosis analysis between drug pairs,the drug association analysis,and the drug clustering analysis of the screened TCM prescriptions.Results Totally 108 prescriptions were included,involving 188 kinds of Chinese materia medica,with a total frequency of 1 322 times.High-frequency drugs included Hedyotis Sinensis,Angelicae Sinensis Radix,Visci Herba,Curcumae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.The medicinal properties were mainly cold,mild and warm,and the tastes were mainly bitter,sweet and pungent,and the main meridians were liver meridians,spleen meridians,kidney meridians and stomach meridians.There were 9 pairs of high frequency drug combinations in drug association,such as Curcumae Radix-Polygoni Orientalis Fructus,Visci Herba-Curcumae Rhizoma.In the correlation analysis of drug disease,the ones with higher correlations include"stomachache-Salviae Miltiorrhizae Radix et Rhizoma""abdominal mass-Paeoniae Radix Rubra and Citri Reticulatae Pericarpium""tinnitus-Adenophorae Radix,Lycii Fructus,Visci Herba""prolonged sublingual collaterals-Curcumae Rhizoma,Polygoni Orientalis Fructus,Salviae Miltiorrhizae Radix et Rhizoma"and so on.Drug clustering could be divided into three potential drug clusters.Conclusion Professor Qian Ying often uses heat-clearing drugs,tonifying drugs,and promoting qi and blood circulation drugs to treat liver cancer,with Huqi Powder as the main formula and modified according to the syndromes.Clearing heat and detoxifying,soothing liver and relieving depression,removing blood stasis and regulating collatrals are used to treat its symptoms,and tonifying qi and invigorating spleen,regulating liver and nourishing liver and kidney are used to treat its essence.

Objective:To explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge.Methods:This study was a retrospective cohort study that included 268 children with bacterial meningitis who were discharged from the infectious medicine ward of Beijing Children′s Hospital from September 2018 to September 2023. The children were managed with a multidisciplinary collaborative comprehensive healthcare management model after discharge. Outpatient data at 1 month and 6, 12 and 24 months after discharge were collected, including (height, weight, body mass index, nutritional feeding status, hearing and vision screening results, Gesell developmental assessment results and intervention guidance services. The follow-up interval or frequency was dynamically adjusted or increased according to the child′s situation. The paired sample t-test and chi square test were applied to compare the differences in Gesell developmental quotient (DQ) and developmental delay rate between the first and last assessments to preliminarily explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge. Results:All the 268 children completed their first assessment one month after discharge, and 37 children were found to have abnormal physical growth, mainly obesity (28 children), and another 9 children were malnutrition. Nutritional intervention and feeding guidance services were provided to all the 37 children, and as of the last follow-up, 20 children′s physical growth evaluations had turned normal. A total of 188 children completed at least 2 developmental assessments, with an interval of (14.2±9.4) months between the first and last assessments (range: 3.1-49.5 months). The DQ values of in the energy region of adaptability, gross motor skills, fine motor skills, language, and personal social skills at the last assessment were significantly higher than those at the first assessment [(91.93±13.28) vs (80.73±15.96) points, (91.69±12.96) vs (78.31±16.58) points, (89.32±16.11) vs (80.68±15.63) points, (90.10±16.65) vs (82.04±18.43) points, (92.01±14.05) vs (77.82±17.42) points]; moreover, the rates of developmental delay in each energy region were significantly lower than those at the initial assessment (9.6% vs 35.1%, 9.6% vs 42.0%, 18.1% vs 33.0%, 13.3% vs 31.9%, 9.6% vs 42.0%) (all P<0.05). Among the 200 children who completed the hearing screening, 18 were found with hearing abnormalities, and 2 were diagnosed with hearing loss in the Otolaryngology Department. Among 217 children who completed vision screening, 23 had abnormalities, and 5 were diagnosed with ophthalmic abnormalities in Ophthalmology Department (2 with strabismus, 2 with refractive errors, and 1 with optic nerve injury). Two children were found to have autism-like behavior during monitoring, and were referred to a developmental behavior clinic to be diagnosed with autism spectrum disorder and were given early diagnosis and intervention guidance. Conclusion:The comprehensive healthcare management model for children with bacterial meningitis after discharge can integrate clinical and healthcare resources, which is beneficial for improving the prognosis and enhancing the quality of life for children with special health status.