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

ObjectiveBased on the experience of traditional quality evaluation， the quality of Atractylodis Macrocephalae Rhizoma（AMR） with different production methods such as direct seeding， transplanting after seedling raising， topping and non-topping， and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining， and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides， oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography（UPLC）， and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）. ResultIn terms of traits， the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck， strong sweetness and clear aroma" recorded in ancient materia medica， followed by the 3-year-old AMR with topping after transplanting， while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect， the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang， the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition， the contents of 70% ethanol extract， fructose， glucose， sucrose， 1-kestose， atractylenolide Ⅰ， chlorogenic acid， neochlorogenic acid， cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples（P<0.05）. The contents of cellulose， 70% ethanol extract， sucrose， atractylenolide Ⅰ， atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate（P<0.05）， while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting， direct seeding and without topping（P<0.05）. ConclusionUnder the current mainstream production mode， too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield， but the accumulation of sweet substances， fragrant substances and fiber substances is insufficient， which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it， it is suggested to revise the quality standard of AMR， supplement the quantitative analysis of secondary metabolites， and strengthen the production of imitation wild AMR.

BACKGROUND:Currently,there have been a variety of conservative and surgical treatment plans for spontaneous osteonecrosis of the knee,achieving excellent results.However,a broad consensus on indication and guide of surgical treatment has not been announced.In clinical practice,there is still a misunderstanding that unicondylar replacement or total knee arthroplasty should be performed upon the discovery of spontaneous osteonecrosis of the knee,while an urgent need for universal access to the concept of stepwise therapy. OBJECTIVE:To summarize and find the factors leading to the poor effect of conservative treatment in spontaneous osteonecrosis of the knee,which occurred on the medial femoral condyle,from the literature and clinical cases,at the same time,combined with the Koshino stage,to propose the strategy of stepwise spontaneous osteonecrosis of the knee treatment on the medial femoral condyle. METHODS:A systematic search of the literature database was conducted to summarize the factors leading to poor outcomes of conservative treatment in spontaneous osteonecrosis of the medial femoral condyle.Meanwhile,according to the Clinical&Health Records for analytics&Sharing system,the cases receiving conservative and surgical treatment in spontaneous osteonecrosis of the medial femoral condyle in the Department of Orthopedics of Guangdong Provincial Hospital of Chinese Medicine from January 2017 to January 2023 were analyzed retrospectively,then the causes of success and failure in typical cases were summarized and analyzed. RESULTS AND CONCLUSION:(1)Early diagnosis and treatment of spontaneous osteonecrosis of the knee were very important for prognosis.For sudden knee pain in some patients,if no obvious abnormality was found in the X-ray examination,and the symptoms persisted and could not be relieved for more than 1 week,an MRI examination was recommended to detect early spontaneous osteonecrosis of the knee.(2)The X-ray images of Koshino stage 1 and stage 2 of spontaneous osteonecrosis of the medial femoral condyle were difficult to be distinguished,which needed to be probed by MRI.MRI images of Koshino stage 1 were mainly characterized by bone marrow edema,and an osteonecrosis area with a clear boundary was not formed,while MR images of Koshino stage 2 showed a necrotic area with a clear boundary.(3)Five factors leading to the poor effect of conservative treatment on spontaneous osteonecrosis of the medial femoral condyle were summarized:a.The necrotic area was＞5 cm2;b.The necrotic area accounted for more than 40%of the condyle;c.relative compression percentage of medial meniscus≥33%(with or without medial meniscus injury and subchondral bone marrow edema);d.MRI depth of necrotic area(anterior-posterior diameter of sagittal necrotic area)＞20 mm;e.varus deformity of lower limb＞6°.(4)Conservative treatment of spontaneous osteonecrosis of the knee in Koshino stage 1 was good.For spontaneous osteonecrosis of the knee in Koshino stage 2,conservative treatment was preferred or combined with drilling decompression.If there was no relief or improvement of symptoms or in MRI after 3 months,while the patient had any of the previous five factors,then knee preservation surgery should be considered.For spontaneous osteonecrosis of the knee in Koshino stage 3 and stage 4,knee preservation surgery should be selected based on the previous five factors,including age,gender and activity level of the patient.Total knee arthroplasty was used for spontaneous osteonecrosis in Koshino stage 4,which was associated with symptomatic patellofemoral arthritis,valgus alignment,or necrotic area,which greatly affected the stability of unicondyle prosthesis.

Objective:To investigate the mechanism of tumor necrosis factor alpha-induced protein 3 ( Tnfaip3) gene affecting the intestinal inflammation in mice with dextran sulfate sodium (DSS) -induced colitis by regulating mitochondria. Methods:Female Tnfaip3 heterozygous deficiency ( Tnfaip3 +/-) mice ( n = 14) and wild-type (WT) mice ( n = 14) were collected and divided into 4 groups including wild type (WT) group, colitis model (WT-DSS) group, Tnfaip3 heterozygous deficiency ( Tnfaip3 +/-) group, Tnfaip3 heterozygous deficiency colitis model ( Tnfaip3 +/--DSS) group, with 7 mice in each group. Mice colitis in WT-DSS and Tnfaip3 +/--DSS groups were induced by drinking 3% DSS water for 7 days, while mice in WT and Tnfaip3 +/- groups were treated with tap water. Body weight and disease activity index (DAI) were evaluated daily. The mice were sacrificed after 7 days of modeling, the colon length was measured, the colon tissue damage was observed under the microscope, and the colon histopathological score was evaluated. The mRNA expressions of inflammatory factors as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and nuclear factor κB (NF-κB) in colon tissue were detected by quantitative real-time PCR. Oxidative stress indicators such as malonic dialdehyde (MDA), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in colon tissue were detected. Transmission electron microscopy was used to observe the structures of mitochondria, lysosomes, and autophagic mitochondria, and calculate the numbers. Mitochondrial membrane potential JC-1 and adenosine-triphosphate (ATP) levels were detected, and Western blot was used to detect the expressions of mitophagy-related proteins PINK1, P62, and LC3B Ⅱ/LC3B Ⅰ in mitochondria and cytoplasm. Results:The survival rate of mice in all groups was 100%. Compared with WT group, the mice in Tnfaip3 +/- group had lower body weight, shorter colon and higher histopathological scores (all P < 0.05). Compared with WT-DSS group, the mice in Tnfaip3 +/--DSS group had lower body weight, higher DAI score, shorter colon, higher histopathological score, and higher mRNA expressions of inflammatory factors TNF-α, IL-1β and NF-κB in colon tissues (all P < 0.05). MDA level in colon tissues of Tnfaip3 +/- mice was higher than that of WT mice ( P < 0.05). Compared with WT-DSS group, the MDA level in Tnfaip3 +/--DSS group was higher, the levels of T-AOC, GSH-PX and SOD were lower (all P < 0.05). Compared with WT-DSS group, Tnfaip3 +/--DSS mice had more severe intestinal disordered mitochondrial structure, less mitochondrial number, higher mitochondrial membrane potential JC-1 level and lower mitochondrial ATP content, more number of lysosomes and autophagic mitochondria and higher expressions of proteins such as PINK1, P62 and ratio of LC3BⅡ/LC3BⅠ in mitochondria and cytoplasm (all P < 0.05) . Conclusion:Tnfaip3 gene may play a protective role in intestinal inflammation of colitis mice by regulating oxidative stress, mitochondria damage and mitophagy.

Objective:To investigate the mechanism of tumor necrosis factor alpha-induced protein 3 ( Tnfaip3) gene affecting the intestinal inflammation in mice with dextran sulfate sodium (DSS) -induced colitis by regulating mitochondria. Methods:Female Tnfaip3 heterozygous deficiency ( Tnfaip3 +/-) mice ( n = 14) and wild-type (WT) mice ( n = 14) were collected and divided into 4 groups including wild type (WT) group, colitis model (WT-DSS) group, Tnfaip3 heterozygous deficiency ( Tnfaip3 +/-) group, Tnfaip3 heterozygous deficiency colitis model ( Tnfaip3 +/--DSS) group, with 7 mice in each group. Mice colitis in WT-DSS and Tnfaip3 +/--DSS groups were induced by drinking 3% DSS water for 7 days, while mice in WT and Tnfaip3 +/- groups were treated with tap water. Body weight and disease activity index (DAI) were evaluated daily. The mice were sacrificed after 7 days of modeling, the colon length was measured, the colon tissue damage was observed under the microscope, and the colon histopathological score was evaluated. The mRNA expressions of inflammatory factors as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and nuclear factor κB (NF-κB) in colon tissue were detected by quantitative real-time PCR. Oxidative stress indicators such as malonic dialdehyde (MDA), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in colon tissue were detected. Transmission electron microscopy was used to observe the structures of mitochondria, lysosomes, and autophagic mitochondria, and calculate the numbers. Mitochondrial membrane potential JC-1 and adenosine-triphosphate (ATP) levels were detected, and Western blot was used to detect the expressions of mitophagy-related proteins PINK1, P62, and LC3B Ⅱ/LC3B Ⅰ in mitochondria and cytoplasm. Results:The survival rate of mice in all groups was 100%. Compared with WT group, the mice in Tnfaip3 +/- group had lower body weight, shorter colon and higher histopathological scores (all P < 0.05). Compared with WT-DSS group, the mice in Tnfaip3 +/--DSS group had lower body weight, higher DAI score, shorter colon, higher histopathological score, and higher mRNA expressions of inflammatory factors TNF-α, IL-1β and NF-κB in colon tissues (all P < 0.05). MDA level in colon tissues of Tnfaip3 +/- mice was higher than that of WT mice ( P < 0.05). Compared with WT-DSS group, the MDA level in Tnfaip3 +/--DSS group was higher, the levels of T-AOC, GSH-PX and SOD were lower (all P < 0.05). Compared with WT-DSS group, Tnfaip3 +/--DSS mice had more severe intestinal disordered mitochondrial structure, less mitochondrial number, higher mitochondrial membrane potential JC-1 level and lower mitochondrial ATP content, more number of lysosomes and autophagic mitochondria and higher expressions of proteins such as PINK1, P62 and ratio of LC3BⅡ/LC3BⅠ in mitochondria and cytoplasm (all P < 0.05) . Conclusion:Tnfaip3 gene may play a protective role in intestinal inflammation of colitis mice by regulating oxidative stress, mitochondria damage and mitophagy.

Objective     To summarize the surgical treatment experience in neonates with coarctation of the aorta (CoA) and aortic arch hypoplasia (AAH). Methods     The neonates with CoA and AAH who underwent surgical treatment in the Department of Pediatric Cardiac Surgery of Guangdong Provincial People's Hospital from 2013 to 2020 were retrospectively enrolled. The postoperative complications, long-term survival rate, and freedom from aortic reobstruction were analyzed. Patients undergoing extended end-to-end anastomosis were allocated into an extended end-to-end group, those undergoing extended end-to-side anastomosis into an extended end-to-side group, and those undergoing pulmonary autograft patch aortoplasty into a patch aortoplasty group. Results     Finally 44 patients were  enrolled, including 37 males and 7 females, aged 5.00-30.00 (19.34±7.61) days and weighted 2.00-4.50 (3.30±0.60) kg. There were 19 patients of extended end-to-end anastomosis, 19 patients of extended end-to-side anastomosis, and 6 patients of pulmonary autograft patch aortoplasty. The mean values of the Z scores of the proximal, distal, and isthmus of the aortic arch were –2.91±1.52, –3.40±1.30, and –4.04±1.98, respectively. The mean follow-up time was 45.6±3.7 months. There were 2 early deaths and no late deaths. Aortic reobstruction occurred in 8 patients, and 3 patients underwent reoperation intervention. The 5-year rate of freedom from reobstruction was 78.8%. The Cox multivariable regression analysis showed that the related factors for postoperative reobstruction were the Z score of the preoperative proximal aortic arch (HR=0.152, 95%CI 0.038-0.601, P=0.007) and the postoperative left main bronchus compression (HR=15.261, 95%CI 1.104-210.978, P=0.042). Conclusion     Three surgical procedures for neonates with CoA and AAH are safe and effective, but the aortic reobstruction rate in long term is not low. The smaller Z score of the preoperative proximal aortic arch and the postoperative left main bronchus compression are risk factors for long-term aortic reobstruction.

  Objective  To summarize the clinical characteristics and RNF216 gene mutation of a patient with Gordon Holmes syndrome (GHS), and to improve the understanding of the genetic and clinica characteristics of this disease through literature review.  Methods  We collected the clinical data of the patient with GHS, extracted the DNA from 2 mL peripheral venous blood of the patient and his parents for whole exome gene detection, and then we analyzed the clinical and genetic characteristics of all previously reported patients with RNF216 gene mutation.  Results  The young male patient was short in stature at sixyearsold and was diagnosed growth hormone deficiency.He had no secondary sexual characteristics by the age of 15 and was diagnosed hypogonadal hypogonadism.After the age of 22, he gradually developed abnormal gait and had progressive decline in speech, motor, and cognitive functions.Whole exome sequencing revealed a homozygous, nonsense mutation c.1549C>T (p.R517*) in the RNF216 gene.His parents were consanguineous and were heterozygous carriers of the mutations with phenotypic normality.Combined with literature review and this case report results showed that a total of 21 patients of the disease in the world and among them 15 had pathogenic variants of RNF216 gene mutation.7 of the 15 had truncated mutations, 5 had missense mutations, and 1 synonym mutation, 1 splice mutation, and 1 deletion mutation respectively.RNF216 gene mutation can be seen in neurodegenerative diseases with multiple overlapping symptoms of GHS, Huntington-like disease, and 4H syndrome.The main clinical manifestations are hypogonadotropic hypogonadism and early-onset progressive neurological dysfunction in adolescence or early adulthood.The median age of onset of neurological symptoms is 28 years old, featuring cerebellar ataxia, dysarthria, and cognitive impairment, as well as imaging manifestations of extensive white matter lesions and cerebellar atrophy.  Conclusions  The mutation of RNF216 gene can cause GHS.Genetic testing is helpful to the diagnosis and treatment of rare diseases.

OBJECTIVES: With the continuous generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pressure of epidemic prevention and control continues to increase in China. Omicron with stronger infectiousness, immune escape ability and repeated infection ability spread to many countries and regions around the world in a short period of time. China has also successively reported cases of imported Omicron infections. This study aims to understand the epidemiological characteristics of Omicron variant via analyzing the epidemiological characteristics of imported patients with Omicron in Hunan Province, and to provide reference for preventing and controlling the imported epidemics. METHODS: The clinical data of imported patients with coronavirus disease 2019 admitted to Hunan Province from December 16 to December 31, 2021 were retrospectively collected. The epidemiological information, general information, clinical classification, clinical symptoms, vaccination status, and lung CT were analyzed. Nasopharyngeal swabs and blood samples were collected. Virus nucleic acid was detected by magnetic beads method using SARS-CoV-2 detection kit. Ct values of ORF1ab gene and N gene were compared between asymptomatic infected patients and confirmed patients. The specific IgM and IgG antibodies were detected by chemiluminescence assay using SARS-CoV-2 IgM test kit and SARS-CoV-2 IgG test kit, respectively. Ct values of IgM and IgG antibodies were compared between asymptomatic infected patients and confirmed patients. RESULTS: Seventeen patients with Omicron variant infection were treated in Hunan, including 15 confirmed patients (5 common type and 10 mild type) and 2 asymptomatic infection patients. The 17 patients were all Chinese, they were generally young, and 16 were male. There were 9 patients with diseases. Of them 3 patients had respiratory diseases. All 17 patients had completed the whole process of vaccination, but only one person received a booster shot of SARS-CoV-2 vaccine. The clinical manifestations of the patients were mild, mainly including dry/painful/itchy throat, cough, and fatigue. The total protein and creatine in the asymptomatic infection and confirmed cases infected with Omicron variant were all within the normal range, but other biochemical indicators were abnormal. There were the significant differences in C-reactive protein and fibrinogen between asymptomatic infection and confirmed patients (both P<0.05). There were more patients with elevated C-reactive protein in confirmed patients than without confirmed ones. The detection rate of specific IgM and IgG antibodies on admission was 100%, and there was no significant difference in the specific antibody levels between asymptomatic infection and confirmed patients (P>0.05). There were no significant differences in Ct values of ORF1ab gene and N gene (21.35 and 18.39 vs 19.22 and 15.67) between the asymptomatic infection and the confirmed patients (both P>0.05). Only 3 patients had abnormal lung CT, showing a small amount of patchy and cord-like shadows. One of them had no abnormality on admission but had pulmonary lesions and migratory phenomenon after admission. CONCLUSIONS The patients with Omicron variant tend to be young people and have milder clinical symptoms, but the viral load is high and the infectiveness is strong. Therefore, the timely identification and effective isolation and control for asymptomatic infections and confirmed patients with mild symptoms are extremely important. In terms of epidemic prevention and control, the government still needs to strengthen the risk control of overseas input, adhere to normalized epidemic prevention and control measures, to effectively control the source of infection, cut off the route of transmission, and protect vulnerable people.
Asymptomatic Infections ; C-Reactive Protein ; COVID-19/virology* ; COVID-19 Vaccines ; China/epidemiology* ; Female ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Male ; Retrospective Studies ; SARS-CoV-2

ObjectiveTo summarize and compare the main traditional Chinese medicine （TCM） syndromes of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） carriers to provide references for the syndrome evolution and syndrome differentiation of SARS-CoV-2 infection. MethodThe TCM medical records of imported and local cases of infection with Delta and Omicron variants of SARS-CoV-2 in Changsha since September 23， 2021 to March 27， 2022 were collected， including 18 Delta variant cases and 36 Omicron variant cases. Their TCM diagnosis information and TCM pathogenesis were analyzed and compared. ResultThe common manifestations in Delta variant cases were cough， fever， chest distress/shortness of breath， sore muscles， nausea， dry mouth， dry or sore throat， thick and greasy tongue coating， and rapid and slippery pulse. The predominant pathogenesis was dampness-heat in the upper-energizer and heat stagnation in the lesser Yang combined with dampness. The occurrence of chest distress/shortness of breath， greasy tongue coating， slippery pulse， and the proportion of dampness-heat in the upper-energizer syndrome were higher in Delta variant cases than in Omicron variant cases （P<0.05）. The common manifestations in Omicron variant cases were itchy and sore throat， nasal congestion， running nose， fever， mild aversion to cold， dry mouth， dizziness， slightly reddish tongue with thin white coating， and rapid or wiry pulse. The predominant pathogenesis was wind-dryness invading defensive exterior， and heat stagnation in the lesser Yang. The occurrence of white-coated tongue and the proportion of wind-dryness invading defensive exterior syndrome were higher in Omicron variant cases than in Delta variant cases （P<0.05）. ConclusionThere are certain differences in TCM syndromes and the corresponding pathogenesis between Delta variant and Omicron variant cases in Changsha， Hunan. The Delta variant of SARS-COV-2 tends to induce dampness-heat syndrome， whereas Omicron variant infection tends to elicit wind-dampness syndrome， which is expected to provide a reference for the pathogenesis evolution of SARS-COV-2 infection.

We report a case of coronavirus disease 2019 (COVID-19) patient who was cured by oral administration of nirmatrelvir/ritonavir (Paxlovid). The patient was treated with Paxlovid after being first infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 variant. On the 11th day after SARS-CoV-2 nucleic acid test turned negative, SARS-CoV-2 nucleic acid test was positive again, and the threshold of nucleic acid cycle number was equivalent to that of the first infection. The results of two whole gene sequencing showed that it was the same virus strain infection, suggesting that the case was re-positive. Without specific treatment, SARS-CoV-2 nucleic acid detection in nasopharyngeal swab turned negative. It is not uncommon for Paxlovid to recover after treating COVID-19, and most of the patients can recover without specific treatment. However, it is necessary to further study the mechanism that may lead to the recovery of SARS-CoV-2.
Humans ; COVID-19 ; SARS-CoV-2/genetics* ; Administration, Oral ; Nucleic Acids