ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

Aim To investigate the mechanism of treatment of hepatolenticular degeneration with Garde-nia and Rhubarb decoction based on network pharma-cology and animal experiments.Methods The chemi-cal components and target sites of Gardenia and Rhu-barb decoction were retrieved using the Traditional Chi-nese Medicine System Pharmacology Analysis Platform(TCMSP).The disease targets were obtained by searching the databases of DisGeNET,GeneCards.The PPI network of active compound target sites was constructed using the STRING database.GO function and KEGG pathway enrichment analysis were per-formed using the DAVID database to predict the action pathway.A copper-loaded WD rat model was estab-lished by intragastric administration of copper sulfate pentahydrate.A total of 36 rats were randomly divided into the normal group,model group,penicillamine group and the low,medium and high dose groups of gardenia rhubarb.The relevant indicators and patho-logical changes of liver tissue were detected in WD rats.Results Network pharmacology screening identi-fied 68 potential active components of Gardenia and Rhubarb Decoction,30 intersection targets of diseases and drugs,involving key targets such as TNF,IL10,IGF1,IL1B,TP53,CASP3,PPARG,IL6,CXCL8,IL1A,TGFB1,mainly related to signal pathways such as MAPK,AGE-RAGE signaling pathway in diabetic complications.In the animal experiments,compared with the normal group,the urine copper,liver copper,blood copper,liver coefficient,serum and liver ALT,AST,TNF-α,CASP3,P53 levels in the model group rats significantly increased(P＜0.05);hepatocyte swelling,cytoplasm loose reticular appearance,feath-er-like degeneration and reticular necrosis were ob-served in liver tissue pathology;compared with the model group,the urine copper,liver copper,blood copper,liver coefficient,serum and liver ALT,AST,TNF-α,CASP3,P53 levels in the penicillamine group and Gardenia and Rhubarb decoction groups were sig-nificantly reduced(P＜0.05),and the degree of re-ticular necrosis in the rat liver cells in the penicilla-mine group and the Gardenia and Rhubarb decoction group was significantly reduced.Conclusions Garde-nia and Rhubarb decoction has the effect of regulating copper metabolism and reducing liver injury.The mechanism of action may be related to reversing apop-tosis and downregulating protein expression of TNF-α,CASP3,P53 in MAPK signaling pathway.

Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P＜0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P＜0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P＜0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.

Objective To investigate the high-frequency ultrasonic anatomical features of the adjacent C7 transverse process and its clinical value in stellate ganglion block(SGB).Methods High-frequency ultrasound was applied to obtain ultrasonographic anatomical sonogram features in the plane of bilateral C7 transverse processes in 52 cases(104 sides in total)of healthy adults and then stored for the operator to learn and correctly label each tissue structure.Fifty patients who underwent ultrasound-guided SGB were selected and divided into the BC7 group(25 cases before study)and AC7 group(25 cases after study).The operation time,SGB success rate,number of adjusted needle tips,dosage of anaesthetic and adverse reaction of patients in both group were recorded.Results The main muscles observed in the C7 plane were the longissimus and anterior scalene muscles,the ultrasonographic anatomical relationships of the vagus nerve located in the carotid sheath,the pleura located posterior to the subclavian artery,and the recurrent laryngeal nerve located in the vicinity of the branches of the inferior thyroid artery are described,and the stellate ganglion was illustrated as a flattened hypoechogenic structure visible on the deep surface of the prevertebral fascia in the region of the external cervical longissimus muscle,vertebral artery and vein,and the medial aspect of the anterior oblique muscle,and emanated the sonographic features of several hypoechoic nerve bundles.Ultrasound guided SGB was completed uneventfully in patients of both groups,and all patients developed Horner syndrome,with the SGB success rate of 100%.The operation time[(5.36±1.11)minutes]of patients in the BC7 group was longer than that in the AC7 group[(3.08±0.86)minutes],the number of adjusted needle tips[(4.20±1.00)times]of patients in the BC7 group was more than that in the AC7 group[(2.24±0.87)times],and the dosage of anaesthetic[(1.82±0.28)mL]of patients in the BC7 group was more than that in the AC7 group[(1.64±0.22)mL],all the differences were statistically significant(P<0.05).There was no significant difference in the incidence of adverse reaction between the two groups(P>0.05).Conclusion After ultrasonic learning of adjacent structures through C7 transverse process,SGB is safe and easy to perform.

Vaccines are among the most effec-tive measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases.Adjuvants,serving as auxiliary com-ponents in vaccines,are indispensable in the vac-cine development process.Ideal adjuvants not only enhance the immune response,enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of im-munogens and lowering vaccine production costs.To meet the demands of novel vaccines,many new types of adjuvants have been developed.However,there is still a lack of adjuvants that are safe,effec-tive,easy to prepare,highly pure,and suitable for a variety of vaccines in clinical settings.This article categorizes adjuvants and summarizes their mecha-nisms of action and characteristics,focusing on tra-ditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants.The summary is based on a computer search of data-bases including PubMed,Embase,The Cochrane Li-brary,CNKI(China National Knowledge Infrastruc-ture),VIP Database,and Wanfang Database,using English search keywords such as Adjuvants,Vac-cine,Vaccine Adjuvant,aluminum salts,MF59,AS03,Toll-like receptor agonist,etc.,and corre-sponding Chinese search terms.The aim is to pro-vide references for the development and applica-tion of adjuvants.

Interleukin-35(IL-35)is an important immunosuppressive cytokine that has been shown to play a role in the immune response of various diseases.In this study,we cloned the coding sequence of human IL-35 gene,constructed single subunit expression vectors pXC17.4-p35 and pcDNA3.1(+)-EBI3,and co-transfected CHO-K1 cells to express IL-35 in vitro.No binding was found between subunits of p35 and EBI3.Knobs-into-Holes(KIH)can solve the problem of heavy chain mismatch of heterolo-gous antibodies.Therefore,expression vectors pXC17.4-p35-Fch and pcDNA3.1(+)-EBI3-Fck were constructed by fusing KIH structures on the basis of the original sequences to express the recombinant fu-sion protein of KIH-IL-35.The expression vectors of two subunits were exchanged at the same time to verify the influence of different vectors on the expression level of KIH-IL-35.The analysis of various pro-tein detection methods showed that the correct expression rate of KIH-IL-35 structure was significantly im-proved.Affinity purification of KIH-IL-35 was performed after large amount of expression,and the bind-ing activity of KIH-IL-35 to glycoprotein 130(gp130)was detected by ELISA.The results showed that the binding of KIH-IL-35 to gp130 was concentration dependent.The indirect activity of KIH-IL-35 and M1 cells was detected by cell activity assay.Further results showed that the inhibition rate of M1 cells in-creased in a dose-dependent manner with the concentration of KIH-IL-35.In addition,a method for de-termining IL-35 activity by activated human peripheral blood mononuclear cells was successfully estab-lished.Activated PBMCs increased in a dose-dependent manner with KIH-IL-35 concentration.In sum-mary,this study utilized the KIH-IL-35 model to enhance the expression of recombinant human IL-35 and validated its high activity in vitro,providing new ideas for the study of IL-35 and the recombinant expres-sion of similar heterodimeric cytokines.

Objective:To investigate the risk factors affecting the prognosis of penile cancer after surgery.Methods:We retrospectively analyzed the clinical data on 112 cases of penile cancer treated in Weifang People's Hospital from January 2013 to De-cember 2023.Using the Kaplan-Meier survival curve,χ2 test,Fisher's exact test,and univariate and multivariate Cox risk regression analyses,we compared the clinical characteristics among different groups,and determined the independent prognostic risk factors for cancer-specific survival(CSS)of the patients.Results:The 1-,3-and 5-year CSS rates of the penile cancer patients were 78.2%,66.1% and 63.7%,respectively.Kaplan-Meier analysis indicated a significant correlation of a higher neutrophil-to-lymphocyte ratio(NLR)with a lower CSS rate(P<0.001).Multivariate Cox regression analysis showed high NLR(HR=2.6;95% CI:1.031-6.558;P=0.043)to be an independent risk factor for CSS.Conclusion:Preoperative NLR is an independent risk factor for the prognosis of penile cancer.In addition,older age,farmer or worker occupation,lower education,preoperative lymphocyte-to-monocyte ratio(LMR)≤2.81,preoperative fibrinogen(FIB)≥3.41 g/L,advanced tumor stage and tumor differentiation are associated with the poor prognosis the malignancy.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Objective To investigate the effect of isoliquiritigenin on airway inflammation mice with neutrophil asthma and its possible mechanism.Methods Neutrophil asthma mouse model were established using ovalbumin.Balb/c mice were randomly divided into control group(equal amounts of 0.9％NaCl were given),model group(ovalbumin modeling),DXM group(intraperitoneal injection of 4 mg·kg-1 dexamethasone),experimental-L,-H groups(intraperitoneal injection of 100,200 mg·kg-1 isoliquiritigenin),with 11 mice in each group.Airway resistance of each group of mice was detected within 24 h after the last atomization excitation,and lung tissue and bronchoalveolar lavage fluid were taken;the total cell count was performed by cell counting plate;the cell classification count was performed by Richs-giemsa staining;the levels of inflammatory factors in bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay;Weatern blot assay was used to detect protein expression in lung tissue.Results The airway resistance values of control group,model group,DXM group,experimental-L group and experimental-H group were(0.84±0.08),(3.34±0.34),(1.23±0.15),(2.47±0.19)and(1.54±0.18)cmH2 O·s-1;the total number of white blood cells were(15.03±0.11),(331.20±26.64),(38.73±3.28),(180.35±16.89)and(82.74±10.51)x 104·mL-1;interleukin 17(IL-17)levels were(4.79±0.58),(19.21±2.39),(6.35±0.81),(15.96±1.10)and(9.04±0.65)pg·mL-1;V-set and immunoglobulin domain-containing 4(VSIG4)protein expression levels were 0.67±0.04,0.24±0.04,0.59±0.06,0.37±0.04 and 0.53±0.05;Nod-like receptor family heat protein domain associated protein 3(NLRP3)protein expression levels were 0.24±0.02,0.74±0.07,0.35±0.04,0.65±0.08 and 0.44±0.03,respectively.The above indexes were compared between the model group and the control group,and the above indexes of DXM,experimental-L and experimental-H groups were compared with model group,and the differences were statistically significant(all P＜0.05).Conclusion Isoliquiritigenin may regulate the VSIG4/NLRP3 complex inflammatory pathway,reduce airway resistance,inhibit the release of inflammatory mediators and improve airway inflammation in mice with neutrophil asthma.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.