Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200～220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P＜0.05),shortened MA and decreased Angle values(P＜0.05),extended tail bleeding time(P＜0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P＜0.05),and continuously increasing K+(P＜0.05)and decreasing Na+(P＜0.05)and Ca2+levels(P＜0.05).Additionally,plasma vWF level(P＜0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P＜0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P＜0.05).MR solution resuscitation shortened tail bleeding time(P＜0.05),increased core body temperature(P＜0.05),elevated plasma vWF level(P＜0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P＜0.05),and decreased that of p-Drp1 protein expression(P＜0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

AIM:To observe the effect of acupuncture on adenosine A1 receptor(A1R)in the caudate puta-men(CPu)of complete Freund's adjuvant(CFA)rats,and to explore the potential mechanism of acupuncture in treat-ment of inflammatory pain.METHODS:Sixty-four 6～8-week-old male Wistar rats were randomly divided into saline group,model group(CFA group),CFA+manual acupuncture(MA)group,CFA+solvent dimethyl sulfoxide(DMSO)group,CFA+A1R agonist 2-chloro-N6-cyclopentyladenosine(CCPA)group,CFA+A1R antagonist 8-cyclopentyl-1,3-di-propylxanthine(DPCPX)group,CFA+MA+DMSO group and CFA+MA+DPCPX group.In MA groups,on the 2nd day af-ter modeling,the rats were needled at Zusanli points on both sides,30 min at a time,once per day,for 7 d.Pain threshold of plantar thermal radiation was used to observe the pain response of the rats.The content of cyclic adenosine monophos-phate(cAMP)in the CPu was detected by ELISA.The protein expression and phosphorylation levels of protein kinase A(PKA)and cAMP response element-binding protein(CREB)were detected by Western blot.The expression of A1R in the CPu was detected by immunofluorescence staining.RESULTS:Compared with saline group,CFA modeling signifi-cantly lowered the thermal pain threshold of the rats(P<0.01).Compared with CFA group,the thermal pain threshold of the rats in CFA+MA group and CFA+CCPA group was significantly increased(P<0.05 or P<0.01).Compared with CFA+ MA+DMSO group,the thermal pain threshold of the rats in CFA+MA+DPCPX group was decreased(P<0.05).Compared with CFA group,A1R protein relative expression level and positive cells in the CPu of the rats in CFA+MA group were in-creased(P<0.05 or P<0.01).Compared with saline group,cAMP content and p-CREB protein level in the CPu of the rats in CFA+MA group were decreased(P<0.05).Compared with CFA+DMSO group,cAMP content and p-CREB pro-tein level in CFA+MA+DMSO and CFA+CCPA groups were significantly decreased(P<0.01).Compared with CFA+MA+ DMSO group,the levels of cAMP,p-PKA and p-CREB in CFA+MA+DPCPX group were significantly increased(P<0.05 or P<0.01).CONCLUSION:Acupuncture on bilateral Zusanli can relieve inflammatory pain in CFA rats,and its mech-anism may be related to A1R/cAMP/p-CREB signaling pathway.

Objective:To investigate the clinical application effect of double-layer soft tissue(DLST)suture closure technique in patients with mandible medication-related osteonecrosis of the jaw(MRONJ)of early and medium stages resulted in application of anti-bone-resorptive drugs.Methods:Early to me-dium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking Uni-versity School and Hospital of Stomatology from October 2021 to September 2022 were included.Clinical information of the patients were collected,including primary disease,concomitant disease,medication regimen(drug type,duration of medication),MRONJ stage,clinical symptoms,imaging manifestations,etc.During surgery,after using marginal mandibulae resection to remove the necrotic bone,the wound was closed using DLST closure technique.Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique,the pain score and functional status of the patiens were evaluated.Results:This study totally included 13 patients,12 women and 1 man,aged(66.69±13.14)years.Seven patients had osteoporosis,2 had lung cancer,3 had breast cancer and 1 had prostate cancer among their primary diseases;7 had no concomitant diseases,2 had diabetes melli-tus,2 had cardiovascular disease and 1 had dry syndrome.Intravenous zoledronic acid were used in 9 patients,the average duration was(37.7±20.0)months,and other drugs,such as letrozole tablets were taken in 7 patients at the same time;Denosumab injection was used in 3 patients for an average of(10.3±11.9)months;Alendronate sodium tablets were taken in 5 patients for an average of(55.20± 27.20)months,and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 pa-tients.The average post-operative follow-up was 11.9 months(9 to 17 months),and all the 13 patients were cured without complications,such as pus overflow and so forth.The pre-operative score of Karnof-sky performance status(KPS)in the patients was 68.46±14.05,and the post-operative score was 82.31±15.36,and the difference was statistically significant(P＜0.05).The pre-operative score of visual analogue scale(VAS)in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51,and the difference had statistical significance(P＜0.001).Conclusion:The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the man-dible using anti-bone-resorptive drugs alone,and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection.Simple involvement of the third branch of trigeminal nerve was rare,and so were oral complica-tions such as pulpitis,periodontitis,spontaneous tooth loss,bone necrosis,etc.This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis.We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago,and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication.A few days later,he developed gum pain in the left mandibular posterior tooth area.He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure.Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening.Visible herpes zoster pigmentation and scarring on the left side of the face appeared.The left mandibular posterior tooth was missing,the exposed bone surface was about 1.5 cm x0.8 cm,and the surrounding gingiva was red and swollen,painful under pressure,with no discharge of pus.The re-maining teeth in the mouth were all m degree loosened.Imageological examination showed irregular low-density destruction of the left mandible bone,unclear boundary,and severe resorption of alveolar bone.The patient was diagnosed as left mandibular osteonecrosis.Under general anesthesia,left mandibular le-sion exploration and curettage+left mandibular partial resection+adjacent flap transfer repair were performed.The patient was re-exmained 6 months after surgery,there was no redness,swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced.Unfortu-nately,the patient had complications of postherpetic neuralgia.This case indicate that clinicians should improve their awareness of jaw necrosis,a serious oral complication of trigeminal zoster,and provide ear-ly treatment.After the inflammation was initially controlled,surgical treatment could be considered to remove the necrotic bone,curettage the inflammatory granulation tissue,and extraction of the focal teeth to avoid further deterioration of the disease.

Objective To observe the ameliorative effect of inhibiting acetyl-CoA carboxylase 2(ACC2)on cardiac dysfunction in septic mice and investigate its underlying mechanism.Methods Mouse model of sepsis was established by cecal ligation and perforation.A total of 24 male C57BL/6 mice(aged 8 weeks,weighing 20～25 g)were divided into sham operation group,sepsis group and ND-630+sepsis group.The cardiac specific ACC2 knockout(ACC2△CM)mice were constructed by Cre-LoxP recombinase system,and ACC2flox/flox Myh6-Cre-(ACC2fl/fl)mice were used as control.Several genetically engineered mice(8 weeks old,20～25 g,male)were divided into ACC2fl/fl+sham operation group,ACC2fl/fl+sepsis group,ACC2△CM+sepsis group,ACC2△CM+Mal-CoA+sepsis group,and ACC2△CM+sham operation group according to the random number table method.The contractile function and myofilament calcium sensitivity of cardiomyocytes were measured by a cell microtensiometer.Western blotting was used to detect the expression level of ACC2,and ELISA was employed to measure the level of malonyl-CoA(Mal-CoA)in myocardial tissue.The survival of the mice in 36 h after sepsis was observed.Results Compared with the sham operation group,the contraction amplitude of cardiomyocytes in sepsis group was decreased markedly,and the calcium sensitivity decreased significantly as well(P＜0.05).Based on the ACC2fl/fl+sham operation group,the ACC2△CM+sepsis group showed significant improvement in myocardial contraction compared with the ACC2fl/fl+sepsis group,with the contraction amplitude of cardiomyocytes recovered by 48.1％,and significantly restored calcium sensitivity(P＜0.05).ACC2△CM+Mal-CoA+sepsis group showed a notable decrease in myocardial cell contraction amplitude and a significant decrease in calcium sensitivity when compared to the ACC2△CM+sepsis group(P＜0.05).Compared with the sepsis group,the contraction amplitude of cardiomyocytes in the ND-630+sepsis group increased significantly,and the calcium sensitivity of myofilament also increased(P＜0.05).The expression level of ACC2 protein in the myocardial tissue of mice in the sepsis group increased compared to the sham operation group(P＜0.05).The level of myocardial Mal-CoA in the sepsis group was higher than that in the sham operation group(P＜0.05);Mal-CoA level in the myocardium of ACC2△CM+sepsis group mice was lower than that of sepsis group(P＜0.05).The 36-hour survival rate of the ACC2△CM+sepsis group.mice was 37.5％higher than that of the ACC2fl/fl+sepsis group mice.(P＜0.05).Conclusion Inhibition of ACC2 exerts a protective effect on myocardial contractility and calcium sensitivity in septic mice by reducing Mal-CoA.

Objective:To understand the relationship between the RNA shedding time of SARS-CoV-2 infected persons and the single nucleotide mutation of the virus, the population of infected persons, underlying diseases and other factors, so as to provide more clues for the study of SARS-CoV-2 infection dynamics.Methods:The data of epidemiology, clinical manifestations, and underlying diseases of infected persons in a cluster epidemic of COVID-19 in Jiangsu province from July to September 2021 were collected. Nasopharyngeal swab samples of cases were collected, and the whole genome of the virus was sequenced by second-generation sequencing technology. The online analysis platform was used to judge the virus type and analyze the mutation site, and Cox proportional risk model was used to analyze the relationship between the RNA shedding time of SARS-CoV-2 and various research factors.Results:There were 350 persons who finally obtained the whole genome sequence of the virus in this COVID-19 outbreak, of which 60.3% were female, the median age was 49 years old (interquartile range, IQR: 37-65 years old)), and the median time of virus shedding was 33 days ( IQR, 26-44 days). The whole-genome sequencing analysis showed that compared with the Wuhan reference strain sequence, the infected persons’ sequence had 34~41 nucleotide mutation sites, belonging to VOC/Delta variant (B.1.617.2 evolutionary branch), and C346T, C1060T, T2803C, T7513C, A29681C were the main single nucleotide polymorphisms (SNPs) of this epidemic. Cox regression analysis showed that age, underlying disease, clinical classification, vaccination, SNP T2803C and T7513C had an impact on the RNA shedding time of SARS-CoV-2. The adjusted multivariate Cox regression result showed that age [ HR=0.73, 95% CI (0.55, 0.95)] and T7513C [ HR=0.37, 95% CI (0.18, 0.77)] were still the risk factors for the extension of SARS-CoV-2 RNA shedding time. Conclusions:This study analyzed the effects of the individual factors and viral single nucleotide variations on the time of viral RNA shedding. Those who were older, suffered from hypertension, had more severe clinical symptoms, were not vaccinated or incompletely vaccinated, and had T7513C mutation in the infected virus, had a risk of a long RNA shedding time of SARS-CoV-2, which should be given special attention and follow-up after rehabilitation.

Objectives:To establish a candidate reference method of isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) for the determination of human plasma normetanephrine, and to evaluate the performance of the method. The method was used to quantify the samples of the external quality assessment program, and to initially evaluate the detection status of plasma normetanephrine.Methods:The isotope standard solution of normetanephrine was selected as the internal standard, the gravimetric method was used for sampling, and the standard curve method was used for quantification. Protein precipitation combined with weak cation solid phase extraction was used for pretreatment, and ultra-high liquid chromatography-coupled triple quadrupole mass spectrometry was used for LC/MS analysis. According to the relevant EP documents, the specificity, matrix effect, detection limit, quantification limit, precision, accuracy, and uncertainty of the method were estimated. This method is used to quantify the samples of the 2020 National Center for Clinical Laboratories external quality assessment program of normetanephrine. Taking the average value of this method as the target value, the optimal allowable total error standard of biological variation as the evaluation limit, the quality of the laboratory testing was evaluated.Results:The method had good specificity, and the interferences and matrix effects did not affect the detection results. The detection limit and quantification limit of plasma normetanephrine were 1.08 pg/g and 3.54 pg/g, respectively. The intra-batch coefficient of variation ( CV) and total CV were 0.43%-1.10% and 0.61%-1.42%, respectively. The relative recovery rates were 98.5%～101.9%. The relative expansion uncertainty of the four plasma samples were 3.10%, 2.34%, 2.16%, and 1.73%, respectively. The results of the external quality assessment program showed that the pass rates of the 202013 and 202014 samples were 80% and 85%, respectively. Conclusions:The study established a candidate reference method of ID-LC/MS/MS for the measurement of plasma normetanephrine. The method is accurate, precise and simple, and is expected to be used as a reference method for the determination of plasma normetanephrine, and can be applied to quantify the samples of the external quality assessment program.

Objective:To investigate the clinical outcome of arthroscopic suture-button Bristow procedure using suture-button fixation for treatment of recurrent anterior shoulder instability.Methods:A retrospective case series study was conducted to analyze 28 patients with recurrent anterior shoulder instability admitted to Shanghai Sixth People’s Hospital from March 2015 to September 2018，including 26 males and 2 females，aged 18-36 years ［（24.1 ± 3.2）years］. Preoperative MRI showed Bankart injury and three-dimensional CT showed glenoid bone defect > 15%. The Hill-Sachs injury was found in 27 patients. Arthroscopic Bristow procedure was used to fix coracoid process graft with the suture-button plate and glenoid labial complex was repaired with the suture anchor to treat anterior instability of the shoulder joint. The visual analogue scale （VAS），American shoulder and elbow surgeon （ASES） scale，Constant score and Rowe score were used to evaluate the shoulder joint function preoperatively，at postoperative 3，6，12 months and at the last follow-up. The postoperative infection，neurovascular injury，redislocation and other complications were recorded，and the incidence rate was calculated. The bone resorption and bone healing of coracoid process graft were analyzed by CT.Results:All patients were followed up for 22 - 36 months ［（24.5 ± 6.3） months］. Three months after operation，the VAS，ASES scale and Constant score were not significantly different from those before operation （ P > 0.05）. In comparison，the Rowe score was significantly higher than that before operation （ P < 0.05）. Six and twelve months after operation，the VAS，ASES scale，Constant score and Rowe score were significantly improved from those before operation （ P < 0.05）. At the last follow-up，the VAS decreased from （2.7 ± 1.5）points preoperatively to （0.8 ± 0.3）points，the ASES scale increased from （78.6 ± 12.7）points preoperatively to （92.4 ± 8.4）points，the Constant score increased from （43.4 ± 5.2） points preoperatively to （81.6 ± 6.7） points，the Rowe score increased from （52.3 ± 7.1）preoperatively to （92.7 ± 5.4） points （ P < 0.05）. During the follow-up，there was no infection，neurovascular injury，re-dislocation and other complications. In addition，24 （86%） out of the 28 patient showed healing of coracoid process grafts，and the overall bone resorption rate was （18.4 ± 6.1）%. No patients had glenohumeral joint osteoarthritis. Conclusion:Arthroscopic Bristow procedure using suture-button fixation for treatment of recurrent anterior shoulder instability has advantages of a low rate of postoperative complications and a high union rate，indicating an effective and safe surgical procedure.

Catecholamines include dopamine, norepinephrine and epinephrine. The main metabolites are 3-methoxytyramine, normetanephrine, metanephrine,homovanillic acid and vanillylmandelic acid. Detection of catecholamines and their metabolites is the cornerstone for the diagnosis of neuroendocrine tumors derived from neural crest such as pheochromocytoma, paraganglioma and neuroblastoma. Liquid chromatography tandem mass spectrometry has been widely used in the detection of catecholamines and their metabolites due to its high sensitivity and high specificity. However, the results of liquid chromatography tandem mass spectrometry in different laboratories are quite different and lack comparability. Accurate determination of catecholamines and their mtabolites in plasma and urine is currently a challenge in the field of clinical detectionbecause of their susceptibility to oxidative degradation, presence of numerous interferences and low concentration in plasma and urine samples.