ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Pollinosis is one of the common allergic diseases, and its morbidity continues to increase. Studies have demonstrated that air pollution is a key environmental factor that leads to the increased prevalence of pollinosis. Air pollutants and pollen allergens exert synergistic effects in stimulating allergic responses in susceptible individuals. In this article, we analyzed the relationship between air pollution and pollinosis based on the latest studies, and elaborated potential mechanisms on how air pollution increases the incidence of pollinosis and aggravates allergic reactions. Air pollutants can increase both pollen production and the levels of allergenic proteins, and enhance allergenicity of pollen allergens through structural alterations or chemical modifications. The potential mechanisms of air pollutants exacerbating pollen allergies are as follows: Air pollutants may disrupt the barrier function of the respiratory epithelium and facilitate the penetration of pollen allergens into deeper tissues. Additionally, they may accelerate the process of the release of pollen allergy-related cytokines, promoting T helper 2 (Th2) cell differentiation and exacerbating inflammatory responses in the airways. Given the limitations of existing research, future prospective studies are needed to explore the effects of mixed pollutants and different types of pollutants on pollen, and the response mechanisms of allergy-related cells and cytokines to different pollutant categories. The findings would provide a comprehensive understanding of the impacts of air pollution on pollen allergies and scientific evidence for effective protection of the heath of pollinosis patients.

Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.

Objective To analyze the immune regulation mechanism of C-MET expression in non-small cell lung cancer by transcriptome sequencing technology.Methods The C-MET expression of lung adenocarci-noma cell line(H1993)and lung squamous cell carcinoma cell line(EBC-1)with high C-MET expression was silenced using siRNA molecular interference technology.The differentially expressed genes(DEGs)before and after C-MET silencing were detected using transcriptome sequencing technology.The signal pathways and related genes of the immune microenvironment in which C-MET may participate in regulation were excavated through bioinformat-ics analysis.Finally,the co-culture technique of human immune cells with H1993 and EBC-1 was used to verify the effect of C-MET on immune factors such as INF-γ,INF-β and CXCL-10.Results We detected 505 DEGs in total using transcriptome sequencing.There were 38 differentially expressed genes in the C-MET regulation group before and after H1993,24 upregulated differentially expressed genes,and 14 downregulated differentially expressed genes,respectively.There are a total of 467 differentially expressed genes in the C-MET regulation group of EBC-1,347 upregulated differentially expressed genes,and 121 downregulated differentially expressed genes,respec-tively.KEGG analysis of differential genes suggested that C-MET expression might participate in the regulation of immune cell regulatory factors through the IL-17 signaling pathway,white blood cell differentiation,cytokine receptor activity,cell cycle,cytokine receptor activity,and cytokine-cytokine receptor interaction.The effect of C-MET on immune factor secretion was verified using the co-culture technique of lung cancer cells and human immune cells,and the results of Rt-qPCR assay suggested,the mRNA transcriptional level of INF-γ in PBMC co-cultured with the C-MET high expression group was 77 times that of the low expression group,and the mRNA transcriptional level of CXCL-10 was 1.6 times that of the low expression group.The mRNA transcriptional level of INF--β was twice as high as that of the low expression group.Conclusion C-MET expression may participate in the regulation of tumor surrounding immune microenvironment through IL-17 signaling pathway,leukocyte differen-tiation,and cytokine receptor activity pathway.

BACKGROUND:It was found that moxibustion can inhibit the inflammatory factors in the serum of rats with cerebral ischemia/reperfusion injury,resist oxidative stress,inhibit cell apoptosis,and effectively reduce cerebral ischemia/reperfusion injury. OBJECTIVE:To observe the effects of different moxibustion intervention time on the expression levels of nucleotide binding oligomerization domain-like protein 3 inflammasome(NLRP3),cysteine aspartase(caspase-1),apoptosis-related speck-like protein,exfoliatin-D protein,interleukin-1β and interleukin-18 in rats with cerebral ischemia/reperfusion injury,and to explore its action mechanism. METHODS:SD rats were randomly divided into sham operation group(n=9)and operation group(n=36).The model of focal cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion in the operation group.After successful modeling,the rats in the operation group were further divided into model group,moxibustion 10-minute group,moxibustion 15-minute group and moxibustion 30-minute group,with 9 rats in each group.Rats in the moxibustion 10-minute,15-minute and 30-minute groups were given moxibustion at"Baihui,Dazhui and Zusanli",respectively,once a day for a total of 7 days.The neurological deficits of rats were evaluated by LONGA method.The cerebral infarction was observed by 2,3,5-triphenyltetrazolium chloride staining.The pathological changes of brain tissue were observed by hematoxylin-eosin staining.The contents of interleukin-1β and interleukin-18 in serum of rats in each group were detected by ELISA.Immunohistochemistry and western blot assay were used to detect the expression levels of NLRP3,caspase-1,apoptosis-related spot-like protein and gasdermin D in the ischemic cortex of rats in each group. RESULTS AND CONCLUSION:Compared with the sham operation group,the neurological deficit score of the model group was significantly increased(P<0.01).Compared with the model group,the neurological deficit score of the moxibustion groups was significantly reduced(P<0.01).Compared with the sham operation group,the infarct volume of the model group was significantly increased(P<0.01).Compared with the model group,the infarct volume of the moxibustion groups was significantly reduced(P<0.01);the infarct volume of the rats was smallest in the moxibustion 30-minute group(P<0.05).Compared with the model group,the contents of inflammatory factors interleukin-1β and interleukin-18 in the serum of rats in the moxibustion groups were decreased(P<0.01).Compared with the moxibustion 10-minute group,the contents of inflammatory factors in the serum of rats in the moxibustion 30-minute group were significantly decreased(P<0.05).Compared with the model group,the expression of NLRP3,apoptosis-related spot-like protein,Caspase-1 and gasdermin D protein in the ischemic cortex of the moxibustion groups was significantly decreased(P<0.01).Compared with the moxibustion 10-minute and 15-minute groups,the expression of protein in the moxibustion 30-minute group was significantly decreased(P<0.05).It is concluded that moxibustion at Baihui,Dazhui and Zusanli can reduce cerebral ischemia/reperfusion injury,among which moxibustion for 30 minutes has the best effect,and its mechanism may be related to the inhibition of pyroptosis mediated by NLRP3/Caspase-1 pathway.

Objective:To study the clinical application and complications of umbilical arterial catheterization (UAC) in premature infants.Methods:From January 2021 to December 2022, premature infants with UAC successfully inserted in NICU of our hospital were enrolled. According to birth weight (BW), the infants were assigned into three groups: <1 000 g, 1 000~1 499 g and ≥1 500 g. The perinatal data, UAC usage, UAC-related complications and risk factors of UAC-related complications were retrospectively analyzed.Results:A total of 39 premature infants received UAC, with gestational age 29.3(27.3, 30.4) weeks and BW 1 100 (900, 1 310) g. The insertion length (IL) of UAC was calculated using the average value of two formulas: a, IL (cm) =4×BW (kg) +7; and b, IL(cm) =3×BW (kg)+9. The accuracy of tube end position was determined using chest/abdomen radiography. 30(76.9%) cases had accurate position, 6(15.4%) had higher position and 3(7.7%) had lower position. The proportion of appropriately positioned tube end in <1 000 g, 1 000~1 499 g and ≥1 500 g groups were 80.0%, 76.5% and 71.4%, respectively, without statistically significant differences ( P>0.05) .No significant differences existed among the three groups in UAC duration and UAC routinely removal rate ( P>0.05). 9 cases (23.1%) of UAC were removed for specific reasons, including 4 cases of arterial spasm, 2 cases of withdrawal of treatment, 1 case of tube end displacement, 1 case of abdominal distension and 1 case of death. 21 cases received 1 U/ml heparin (0.9%NaCl solution) 0.5~1 ml/h arterial infusion. 23.8% (5/21) had hypernatremia and the level of sodium became normal after reducing the concentration of NaCl solution. Arterial vasospasm occurred in 4 patients with skin color changes of one side of the lower extremities. After UAC removal, the skin color returned to normal. Conclusions:UAC is helpful and safe for preterm infants, however, its complications should be alerted to.

Objective To explore the application value of ultrasound microvascular imaging combined with shear wave elastography in differentiating thyroid ultrasound image reporting and data system(TI-RADS)4 benign and malignant thyroid nodules.Methods Totally 114 thyroid nodules diagnosed as ACR TI-RADS 4 in Hangzhou traditional Chinese medicine hospital from November 2021 to December 2022 were retrospectively selected.All nodules were examined by ultrasound microvascular imaging and shear wave elastography,and compared with the surgical pathological results to evaluate the diagnostic efficacy of microvascular imaging,shear wave elastography and the combination of the two.Results Among 114 cases of thyroid TI-RADS type 4 nodules,35 cases were benign nodules,79 cases were malignant nodules.The microvascular pattern of malignant nodules was mainly concentrated and interrupted sign and perforator sign.The Emax value of shear wave elastography was statistically significant in differentiating benign from malignant nodules,and the SWE Emax value of malignant nodules was greater than 41.6kPa(P<0.05).The sensitivity,specificity and accuracy of ultrasound microvascular imaging combined with shear wave elastography in the diagnosis of thyroid TI-RADS 4 nodules were 96.20%,65.72%and 86.84%,respectively,and the area under curve(AUC)was 0.810.The sensitivity and accuracy were higher than those of single diagnosis mode,and the difference was statistically significant(P<0.05).Conclusion Ultrasound microvascular imaging combined with shear wave elastography can improve the diagnostic efficiency of benign and malignant thyroid TI-RADS 4 nodules with high diagnostic sensitivity and accuracy,which is helpful for the noninvasive differential diagnosis of such nodules and avoids some unnecessary needle biopsy.

Sepsis is a pathological condition in which the body’s response to infection is dysfunctional and may lead to life-threatening organ failures as one of the leading causes of death worldwide. However，there is still a lack of effective prevention and treatment for sepsis. IL-17A is an inflammatory cytokine produced primarily by activated T cells and is involved in host defense，tissue repair，the pathogenesis of inflammatory diseases，and the progression of cancer. This article reviews the recent research progress on the roles of IL-17A in sepsis-related organ damage，and its potentials as a novel therapeutic target for the clinical treatment of sepsis.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.