This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To investigate the whole genome characteristics of coxsackievirus A4 (CVA4) circulating in Qingdao city.Methods:Four CVA4 isolates circulating in Qingdao city during 2013 to 2015 were selected. Whole genome sequences of these strains were amplified by one-step reverse transcription-polymerase chain reaction (RT-PCR). Sequence alignment and phylogenetic analysis were performed using MEGA7.0 software package. Genetic recombination analysis was performed using similarity plots 3.5.1 software package.Results:Phylogenetic analysis showed that based on the sequences of the whole genome and P1, P2 and P3 regions, HS312/QD/CHN/2013 and HS605/QD/CHN/2014 strains together with the early domestic isolates belonged to the same clade, while FY218/QD/CHN/2015 strain and CV-A4/P1033/2013/China strain collected in Wenzhou in 2013 formed another clade in each phylogenetic tree. HS144/QD/CHN/2014 strain belonged to the same clade as HS312/QD/CHN/2014, HS605/QD/CHN/2014 and the early domestic CVA4 isolates in the phylogenetic tree based on the P1 region, but formed a separate clade in the phylogenetic trees based on the whole genome, P2 region and P3 region. Genetic recombination analysis revealed that there was genetic recombination between HS144/QD/CHN/2014 strain and the CVA2 strain of CV-A2/P373/2013/China isolated in mainland China in 2013 in the region of 2C-3D (5 081-7 301); FY218/QD/CHN/2015 and CV-A4/P1033/2013/China strains were highly homologous and recombination signal sequences were detected in the region of 2A-2B (3 821-4 161) between the two strains and the CVA2 strain of CV-A2/P373/2013/China.Conclusions:The CVA4 isolates circulating in Qingdao city presented obvious genetic diversity at the genome-wide level.

Objective:To evaluate the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of osteoarticular infection.Methods:The clinical data of 37 inpatients aged 32-90 year with osteoarticular infection admitted in the Department of Spine Surgery of Qingdao Chest Hospital from January to December 2019 were retrospectively analyzed. There were 31 cases of spine infection and 6 cases of other joint infection. The tissue samples were obtained from the infected sites through puncture or surgical approach in all patients. The tissue samples were subjected to routine culture of mycobacteria, aerobic bacteria and anaerobic bacteria, respectively. The gene amplification and mNGS were performed for detection of mycobacterium tuberculosis DNA (MTB-DNA). The chi-square test or Fisher’s exact test were used to compare the detection rates of pathogen and simple bacterial infection between mNGS and conventional culture. The conventional culture, mNGS and MTB-DNA amplification detection were performed for all samples; with clinical diagnosis as the gold standard, the diagnostic values of 3 methods were evaluated with receiver operating characteristic curve (ROC). Paired sample t test was used to compare white blood cell(WBC) count, erythrocyte sedimentation rate, C-reactive protein of patients before and after treatment. P<0.05 was considered statistically significant. Results:The pathogens were detected by mNGS for 42 times: bacteria for 39 times (92.8%), fungi for twice (4.8%) and Kirks body for once (2.4%). Among 37 patients there were 29 cases of pure bacterial infection (78.4%), 2 cases of pure fungi infection (5.4%), 1 case of pure Kirks body infection (2.7%), and 5 cases of mixed infection of two or more pathogens (13.5%). The detection rates of mNGS and conventional culture were 100.0% (37/37) and 67.6% (25/37), respectively ( χ2=13.987, P<0.05). The detection rates of mNGS and conventional culture in 29 patients with pure bacterial infection were 100.0% (29/29) and 69.0% (20/29), respectively ( χ2=16.913, P<0.05). The area under the ROC curve (AUC) of conventional culture, mNGS, and MTB-DNA in the diagnosis of osteoarticular tuberculosis infection was 0.958 (95% CI: 0.866-1.000, P<0.05), 1.000 (95% CI: 1.000-1.000, P<0.05) and 0.958 (95% CI: 0.866-1.000, P<0.05). All the 37 patients were treated with anti-infective drugs according to the results of mNGS and conventional culture. Among them, 28 patients received surgical intervention. The patients were followed up until April 30, 2020, 1 patient died. After 3 months of follow-up, the WBC count, erythrocyte sedimentation rate and C-reactive protein were (5.5±1.5)×10 9/L, (41±38)mm/h and (5.0±4.6) mg/L, respectively, which were lower than those before anti-infection treatment [(8.0±2.9)×10 9/L, (79±42)mm/h and(63±52)mg/L] ( t=6.536, 8.302 and 6.373, all P<0.05). Conclusion:The metagenomic next-generation sequencing may have important clinical value in the differential diagnosis of osteoarticular infection.

Objective: To evaluate the effectiveness and safety of the endoscope combined with microscope for the microvascular decompression in hemifacial spasm. Methods: A total of 26 patients underwent endoscope combined with microscopic facial nerve microvascular decompression through retrolabyrinthine approach from January 2013 to December 2016 were retrospectively reviewed in Ear Institute, Shanghai Jiaotong University School of Medicine. Among them, 9 were male and 17 were female, with a mean age of (51.9±11.4) years;15 cases of left side and 11 of right side patients were followed up for 1-3 years. The pre-and post-operative Cohen Classification was used for hemifacial spasm, House-Brackmann Grade for facial nerve function, hearing level and complication rates were reviewed. SPSS 19.0 software was used to analyze the data. Results: All 26 patients were operated successfully. No recurrence was seen during 1-3 year follow-up. Post-operative Cohen Grade were as follows: 25 cases with Cohen Grade I and 1 case with Cohen Grade II. The difference in Cohen grade between pre-and post-operative was statistically significant (Z=-4.87, P<0.01). Post-operative facial nerve function was satisfactory in all patients (House-Brackmann Grade I-II in all patients). No hearing loss was observed. No facial paralysis and other lower cranial nerve dysfunction were observed. No postoperative complications such as cerebrospinal fluid leakage occurred. Conclusions Using an angled endoscope combined with microscope in microvascular decompression in hemifacial spasmis is safe and effective.

Objective To investigate the effects of acupuncture rehabilitation techniques combined with Xingnaojing injection on functional recovery and the plasam level of glial fibrillary acidic protein (GFAP) in patients with severe traumatic brain injury (STBI).Methods Eighty-four patients with STBI admitted to Department of Neurosurgery in Jiuquan People's Hospital from October 2013 to December 2015 were enrolled,they were divided into observation group (44 cases) and control group (40 cases) by random number table,all patients received the routine basic treatment,such as decreasing intracranial pressure,anti-infection,neural nutrition therapy,etc.In addition,the observation group was treated with acupuncture rehabilitation training (each training 50 minutes,1-2 times a day,10 times as a course of treatment,a total of 5 courses) and Xingnaojing injection (in 0.9％ normal saline or 5％ glucose injection 250 mL intravenous infusion,one time a day,10 days as a course of treatment,a total of 3 courses).The evaluation score of Montreal cognitive assessment (MoCA),Modified Barthel index (MBI),Fugl-Meyer assessment (FMA) of motor function score and the plasma levels of GFAP and myelin basic protein (MBP) were measured before and after treatment in the two groups.Results After treatment,the MoCA,MBI and FMA scores were significantly higher in two groups than those before treatment (all P ＜ 0.05),the contents of MBP and GFAP were significantly lower than those before treatment,and the changes in observation group were more significant than those in control group [visual space and execution capability (score):4.99 ± 0.67 vs.3.42 ± 0.73,denomination capability (score):2.98 ± 0.77 vs.2.84 ± 0.47,delayed memory (score):5.76± 0.33 vs.3.87± 2.08,attention (score):6.17± 0.65 vs.4.75 ± 0.81,speech capability (score):3.51 ± 0.46 vs.2.04 ± 0.13,abstract thinking capability (score):2.94 ± 0.27 vs.1.58 ± 0.96,orientation force (score):6.02±0.65 vs.4.88±0.62,FMA score:68.71 ±34.17 vs.41.13 ± 14.82,MBI score:69.12± 10.45vs.37.63±6.11,MBP (μg/L):1.32±0.23 vs.5.31±0.79,GFAP (μg/L):0.19±0.08 vs.0.39±0.04,all P ＜0.05].Conclusions Acupuncture rehabilitation training combined with Xingnaojing injection may obviously improve the cognitive and motor functions in patients suffered from STBI,and clinically the combined treatment is worthwhile to be used extensively.

OBJECTIVE To explore the significance of intraoperative auditory monitoring(IAMA) in surgery of acoustic neuroma and to compare the value of auditory brainstem response(ABR) and cochlear nerve action potential(CNAP) in auditory monitoring.METHODS Retrospective analysis of 12 cases of acoustic neuroma from January 2016 to December 2016 was performed.All patients have a practical hearing(AAO-HNS,grade class a,b),the ABR waveform can be elicited,wave v differentiation,All tumors were removed via posterior sigmoid sinus approach.RESULTS ABR waveform of all patients were prolonged with different degrees of change(0.68±0.41) ms compared with the preoperative data.Amplitude of CNAP diverse in different individuals,with an average prolong compared to the data before operation(0.25±0.16) ms.In all 12 cases,8 (66.7％) patients remained usable hearing after the operation,4 cases(33.3％) failed to have a usable hearing.Among these 4 patients,3 showed disappearance of wave v,1 patient showed wave v latency prolong in the ABR,meanwhile,2 patients showed P1 dissapear,2 patients showed P1 latency prolong in CNAP.The intraoperative auditory monitoring could play a role in preventing the hearing damage in the procedure.Drilling,noise,surgical nerve stretch or thermal injury may cause the hearing damage.A 5 minutes pause could get some degree of regain,with the amplitude rise again.CONCLUSION A combination use of the ABR and CNAP monitoring has a certain significance in surgery of acoustic neuroma.ABR waveform is stable and reliable,but costs longer time;CNAP stack quickly and improve monitoring sensitivity,but waveform varies.Vibration and noise caused by drilling,nerve stretch during operation and heat damage can be monitored timely.Combined use of ABR and CNAP monitoring can enhance the auditory preservation rate during acoustic neuroma surgery.

OBJECTIVE To evaluate the application ofretrolabyrinthine approach in cerebellopontine angel(CPA) region surgeries.METHODS A total of 42 patients underwent microscopic-endoscopic cooperative surgeries for CPA lesions via retrolabytinthine approach were reviewed.They were hospitalized from January 1st 2011 to January 1st 2016 in our institution.The microscopic-endoscopic technique was applied in all surgeries.RESULTS Complete removal was obtained in all tumor resections and satisfactory symptom-relief was achieved in all microvascular decompressions and neurectomies.In cases with acoustic neuroma and cholesteatoma,useful hearing (AAO-HNS classes A,B and C) was obtained in 66.7％(6/9) patients.No facial paralysis and postoperative complications such as cerebrospinal fluid leakage occurred during follow-up.In cranial nerve rhizopathies cases,complete relief was achieved in all patients.No facial paralysis and other lower cranial nerve dysfunction occurred.CONCLUSION With the preservation of labyrinthine structures,the microscopic-endoscopic cooperative surgeries for CPA lesions via retrolabytinthine approach could increase the hearing preservation level without facial nerve injury.Retrolabyrinthine approach is a good option for cranial nerve rhizopathies and tumors smaller than 15 mm in diameter without involvement of the fundus of internal auditory canal in the CPA region.