Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

Background::Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC.Methods::We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies.Results::A total of ten studies were included. The sample size ranged from 8 to 235, with participants’ age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2: 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2: 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2: 59%]). Conclusion::In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence.Registration::PROSPERO, https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022367896.

Objective To analyze the factors affecting the prognosis of patients with knee osteoarthritis,and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators.Methods The clinical data of 234 pa-tients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed,including 126 males and 108 females;age more than 60 years old for 135 cases,age less than 60 years old for 99 cases.Lysholm knee function score was used to evaluate the prognosis of the patients,and the patients were divided into good progno-sis group for 155 patients and poor prognosis group for 79 patients according to the prognosis.The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors.The patients were divided into experimental co-hort and verification cohort,the results of the multiple factor analysis were visualized to obtain a nomogram prediction model,the receiver operating characteristic curve(ROC),calibration curve and decision curve were used to evaluate the model's dis-crimination,accuracy and clinical benefit rate.Results The results of multivariate analysis showed that smoking,pre-treatment K-L grades of Ⅲto Ⅳ,and high levels of interleukin 6(IL-6)and matrix metallo proteinase-3(MMP-3)were risk factors for the prognosis of patients with knee osteoarthritis.ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95％CI(0.742,0.866)]and 0.786[(95％CI(0.678,0.893)],re-spectively.The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points,respectively.When the threshold probability value in the decision curve was set to 31％,the clinical benefit rates of the experimental cohort and validation cohort were 51％and 56％,respectively.Conclusion The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance,and can provide a reference for taking targeted measures to improve the prognosis of patients.

Objective To compare clinical efficacy of robot-assisted(RA)and remote sensing navigation alignment(RSNA)system-assisted total knee arthroplasty(TKA).Methods From March 2023 to June 2023,60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis(KOA)were admitted and divided into RSNA group and RA group according to different treatment methods,with 30 patients in each group.There were 5 males and 25 females in RSNA group,aged from 56 to 81 years old with an average of(66.33±7.16)years old;body mass index(BM1)ranged from 19.87 to 38.54 kg·m-2 with an average of(28.40±6.18)kg·m-2;the courses of disease ranged from 5 to 36 months with an average of(18.20±8.98)months;RSNA system was used to assist the positioning of osteotomy.There were 7 males and 23 females in RA group,aged from 55 to 82 years old with an average of(67.83±8.61)years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an aver-age of(28.01±4.89)kg·m-2;the courses of disease ranged from 3 to 33 months with an average of(17.93±9.20)months;RA was performed.Operation time,incision length,latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups.Hip-knee ankle angle(HKAA),HKAA deviation,lateral distal femoral angle(LDFA),medial proximal tibial angle(MPTA)and posterior tibial slope(PTS)were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index(WOMAC)and Knee Society score(KSS)were used to evaluate functional recovery before operation,3 and 6 months after operation.Results The operation was performed successfully in both groups,and there were no serious complications such as vascular and nerve injury during operation.The wound healed well at stage Ⅰafter operation,and the follow-up time was 6 months.The operation time,latent blood loss at 2 weeks after operation and inci-sion length in RSNA group were(94.35±5.75)min,(130.54±17.53)mland(14.73±2.14)cm,respectively;while(102.57±6.88)min,(146.33±19.47)ml and(16.78±2.32)cm in RA group,respectively.RSNA group was better than RA group(P＜0.05).No deep vein thrombosis occurred in both groups at 2 weeks after operation,5 patients occurred intermuscular vein throm-bosisin in RSNA group and 8 patients in RA group,the difference was not statistically significant(P＞0.05).In RSNA group,HKAA,LDFA and MPTA were(173.00±5.54)°,(86.96±3.45)°,(82.79±3.35)° before operation,and(178.34±1.85)°,(89.92±0.42)°,(89.84±0.73)° at 1 week after operation,respectively.In RA group,HKAA,LDFA and MPTA were(173.31±6.48)°,(87.15±3.40)° and(82.99±3.05)° before operation,and(178.52±1.79)°,(90.03±0.39)° and(90.15±0.47)° at 1 week after operation,respectively.HKAA,LDFA and MPTA were significantly improved in both groups at 1 week after oper-ation(P＜0.05).There were no significant difference in HKAA,LDFA,MPTA and PTS between two groups before operation and 1 week after operation(P＞0.05).There was no significant difference in deviation distribution of HKAA at 1 week after op-eration(x2=2.61 1,P=0.456).There were no significant difference in WOMAC and KSS between two groups before operation,3 and 6 months after operation(P＞0.05),and postoperative WOMAC and KSS at 3 and 6 months between two groups were im-proved compared with those before operation(P＜0.05).Conclusion Both RA and RSNA system assisted TKA could obtain ac-curate osteotomy,RA has higher surgical accuracy,RSNA system assisted operation has less trauma,and operation is simpler.

Objective To explore clinical accuracy of remote sensing navigation alignment(RSNA)system in total knee arthroplasty(TKA)and its influence on postoperative clinical efficacy.Methods From May 2021 to May 2022,60 knee os-teoarthritis(KOA)patients with Kellgren-Lawrence(K-L)grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods,and 30 patients in each group.There were 6 males and 24 females in RSNA group,aged from 55 to 86 years old with an average of(68.06±8.23)years old;body mass index(BMI)ranged from 22.15 to 34.58 kg·m-2 with an average of(28.20±3.01)kg·m-2;the courses of disease ranged from 2 to 60 months with an average of(18.80±14.80)months;13 patients with grade Ⅲ and 17 patients with grade Ⅳaccording to K-L grading.In traditional operation group,there were 8 males and 22 females,aged from 57 to 85 years old with an average of(67.26±6.32)years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of(27.49±2.32)kg·m-2;the courses of disease ranged from 3 to 60 months with an average of(21.30±16.44)months;14 patients with grade Ⅲ and 16 pa-tients with grade Ⅳ according to K-L grading.Western Ontario and McMaster Universities(WOMAC)osteoarthritis index and Knee Society score(KSS)were used to evaluate functional recovery of patients.Hip-knee-ankle angle(HKAA),distal femoral valgus angle(FVA)and distal fermoral flexion angle(DFFA)were measured before operation.HKAA and HKAA deviation angle were measured at 1 week after operation,and defective rate of lower limb force line,femur prosthesis valgus angle(FP-VA)and femoral prosthesis flexion angle(FPFA),respectively,were calculated.Results There were no serious complications such as vascular and nerve injury during operation,and wound healed at stage Ⅰ.Both groups were followed up for 6 months.There were no significant difference in WOMAC index,KSS,HKAA,FVA and DFFA between two groups before operation(P＞0.05).The force line defect rate,HKAA,HKAA deviation angle,FPVA deviation angle and FPFA of RSNA group were 6.7％,(178.74±1.56)°,(1.25±1.56)°,(1.84±0.16)° and(4.85±2.46)°,respectively;while in traditional operation group were 20％,(176.73±3.46)°,(3.27±3.46)°,(2.44±0.26)°,(6.60±1.86)°;the difference between two groups were statistically sig-nificant(P＜0.05).There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation(P＞0.05).Conclusion RSNA system could reduce defective rate of lower limb force line,FPVA deviation angle and FPFA after TKA,which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Objective To investigate the feasibility and clinical effect of the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy.Methods Between June 2018 and September 2022,the medical records of 15 patients with Neer Ⅱ b distal clavicular fracture treated with locking plate under arthroscope were retrospectively analyzed,including 9 males and 6 females,aged from 25 to 57 years old with an average of(42.50±7.75)years old,5 left shoulder,10 right shoul-der,and duration of the disease ranged from 4 to 7 days with an average of(5.16±0.98)d.Visual analog score(VAS),Con-stant-Murley shoulder joint score scale and Neer standard score were used before operation,1 month after operation and the last follow-up.Results All patients successfully completed the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy,with the operation time ranging from 0.3 to 1.0 h with an average of(0.55±0.24)h.All patients were healed at stage Ⅰ.The follow-up time ranged from 6 to 15 months with an average of(9.2±2.8)months.The preoperative VAS score was 7.23±0.67,the Constant-Murley shoulder joint score was(19.57±0.91),and the Neer standard score was(11.27±1.12);The VAS score was(1.56±0.81),the Constant-Murley shoulder joint score was(52.62±1.54),and the Neer standard score was(61.98±2.99)in the first month after operation;At the last follow-up,the VAS was(0.42±0.54),the Constant-Murley shoulder joint score was(91.24±1.97),and the Neer standard score was(93.24±3.38).The difference between VAS,Con-stant-Murley shoulder joint score and Neer standard score was statistically significant at one month postoperative and preoper-ative(P＜0.05),and the difference between the last follow-up visit and one month postoperative was statistically significant(P＜0.05).Conclusion The treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscope can restore the function of shoulder joint,with definite curative effect and feasibility.

This work was aimed at predicting and verifying B-cell epitopes of SARS-CoV-2 E protein through bioinformatics methods,and clarifying the dominant B cell epitopes with mouse polyclonal antibody serum prepared through SARS-CoV-2 re-combinant E protein immunization and human positive serum vaccinated with inactivated SARS-CoV-2 vaccine.The structural and B-cell linear epitopes of SARS-CoV-2 E protein were predicted with SOPMA,Expasy,SWISS-MODEL,IEDB database,and Bepid-2.0 software.Candidate epitopes were expressed as GST-tagged recombinant protein fragments in an E.coli sys-tem,and their immunoreactivity with mouse and human poly-clonal positive serum against SARS-CoV-2 E protein was de-tected by western blotting and indirect ELISA,respectively.The epitope prediction results showed that E protein contained linear B cell epitopes Ser6-Val14 and Tyr57-Pro71,and the conformational epitopes of Glu8-Val12,Leu39-Tyr59,and Ser60-Leu65.The GST tagged recombinant E protein fragments of E1 and E3,containing Ser6-Val14 and Tyr57-Pro71 epitopes,respectively,as well as E2 without an epitope sequence as a control,were expressed in an E.coli expression system and successfully purified with an Ni-NTA column.Western blotting and indirect ELISA analysis indicated that all mouse and human SARS-CoV-2 positive sera positively reacted with only E1 and E3 proteins,but negatively reacted with E2 protein,thus indicating that the corresponding epitope prediction with Ser6-Val14 and Tyr57-Pro71 was correct.This study successfully predicted and preliminarily identified two linear B cell epitopes of SARS-CoV-2 E protein,thus providing a reference for the preparation of new coronavirus vaccines and the analysis of immune response characteristics.

Vesicular glutamate transporter 2(VGlut2)is expressed in the PVN of the hypothalamic paraventricular nucleus(PVNVG1ut2)as an excitatory neurotransmitter,which regulates food intake and energy metabolism and plays an important role in maintaining homeostasis.However,it is not clear that the upstream and downstream projection network of PVNVGut2 neurons hinders the anal-ysis of glutamatergic neuron circuit function.Anterograde and retrograde tracer viruses were injec-ted into the PVN of VGlut2 mice by stereotactic brain injection technique to find the input and output nuclei of PVNVGlut2 neurons.Anterograde tracing results showed that PVNVGlut2 neurons pro-jected to the downstream medial amygdala(MeAD)and arcuate nucleus(ARC).Retrograde trac-ing results showed that PVNVGlut2 received input from the prefrontal nucleus(Pr),the reticular tegmental nucleus(RtTg),and the hypoglossal nucleus(12N).In addition,VGlut2 was found to be co-expressed with neuronal nitric oxide synthase(nNOS)neurons in the PVN.The anatomical net-work of PVNVG1ut2 neurons was analyzed by virus tracking tool,which laid the anatomical founda-tion for further study on the functional regulation of PVNVGlut2.

Objective:To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor(G-CSF)or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT),and to analyze the length of hospital stay,hospitalization cost and post-transplant survival of the patients.Methods:A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022,the febrile neutropenia,the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed.The length of hospital stay,total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared.Results:A total of 102 cases were included in this study,including 57 cases of multiple myeloma,36 cases of acute leukaemia,7 cases of lymphoma,3 cases of myelodysplastic syndrome,1 case of light chain amyloidosis,and 1 case of POEMS syndrome.47 patients received levofloxacin+G-CSF antibacterial prophylaxis,and 55 patients received G-CSF supportive therapy.In the levofloxacin+G-CSF group,40 cases(85.11％)developed febrile neutropenia,and 13 cases(27.66％)were confirmed as bacterial infection.In the G-CSF group,44 cases(80.00％)developed febrile neutropenia,and 16 cases(29.09％)were bacterial infection.There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups(x2=0.46,P=0.50;x2=0.03,P=0.87).The use rate of intravenous antibiotics in the levofloxacin+G-CSF group was 85.11％(40/47),which was not statistically different from 85.45％(47/55)in the G-CSF group(X2=0.04,P=0.84).The detection rates of levofloxacin-resistant bacteria in the levofloxacin+G-CSF group and G-CSF group were 8.57％(3/35)and 21.43％(6/28),respectively,with no statistical difference(x2=0.65,P＞0.05).The median length and median cost of hospitalization in the levofloxacin+G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan,with no statistically significant differences(t=3.00,P=0.09;t=0.94,P=0.09).Within 90 days after transplantation,two cases(4.26％)died in the levofloxacin+G-CSF group and one case(1.82％)died in the G-CSF group,with no statistically significant difference between the two groups(x2=0.53,P=0.47).Conclusion:Application of levofloxacin+G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.