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

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Objective:To observe the effect of α-synuclein (α-Syn) aggregates incubated with plasma from patients with Parkinson's disease (PD) and multiple system atrophy (MSA) on mitochondrial and lysosomal functions, and further clarify the role of α-Syn in pathological mechanism of PD and MSA.Methods:Human neuroblastoma cells (SH-SY5Y) were treated with 10 μg/mL α-Syn aggregates incubated with phosphate buffered solution (PBS), and plasma from healthy controls (HCs), PD patients, and MSA patients, respectively; and the untreated SH-SY5Y cells were used as control group. Mito-Tracker Red CMXRos fluorescent staining was used to detect the mitochondrial membrane potential, Western blotting was used to detect the cytochrome C (Cyt C) expression in the mitochondria and cytoplasm, and adenosine triphosphate (ATP) test kit was used to detect the intracellular ATP level. In addition, the lysosomal associated membrane protein-1 (LAMP1) expression was detected by Western blotting, and cathepsin B activity was detected by Magic Red fluorescent staining.Results:(1) Effects of different α-Syn aggregates on mitochondrial function damage: compared with the control group, the PBS, HC, PD and MSA groups had significantly decreased relative fluorescent intensity (Mito-Tracker Red CMXRos staining) in the SH-SY5Y intracellular mitochondria ( P<0.05); the PD group and MSA group had significantly decreased relative fluorescent intensity compared with PBS group and HC group ( P<0.05); the MSA group had significantly decreased relative fluorescent intensity compared with the PD group (41.27%±5.97% vs. 60.05%±4.24%, P<0.05). Compared with the control group, the HC, PD and MSA groups had significantly decreased mitochondrial Cyt C protein expression, while the PBS, HC, PD and MSA groups had significantly increased cytoplasmic Cyt C protein expression ( P<0.05); the PD group and MSA group had significantly decreased mitochondrial Cyt C protein expression compared with the PBS group and HC group ( P<0.05); the MSA group had significantly increased cytoplasmic Cyt C protein expression compared with the PBS group ( P<0.05); the MSA group had significantly decreased mitochondrial Cyt C protein expression (51.50%±4.22%) and increased cytoplasmic Cyt C protein expression (199.40%±6.73%) compared with the PD group (65.52%±2.18% and 174.00%±16.18%, P<0.05). Compared with the control group, the PBS group, HC group, PD group and MSA group had significantly decreased ATP level ( P<0.05); the PD group and MSA group had significantly decreased ATP level compared with the PBS group and HC group ( P<0.05); the MSA group had significantly decreased ATP level (1.81±0.13 nmol/mg) compared with PD group (2.96±0.29 nmol/mg, P<0.05). (2) Effects of different α-Syn aggregates on lysosomal functions: compared with the control group, the PD group and MSA group had significantly decreased LAMP1 protein expression ( P<0.05); the MSA group had significantly decreased LAMP1 protein expression (60.74%±7.94%) compared with the PBS group, HC group, and PD group (79.70%±4.34%, P<0.05). Compared with the control group, the PBS, HC, PD and MSA groups had significantly enhanced relative fluorescent intensity of lysosomal cathepsin B ( P<0.05); the PD group and MSA group had significantly enhanced relative fluorescent intensity of lysosomal cathepsin B compared with PBS group and HC group ( P<0.05); the MSA group had significantly increased relative fluorescent intensity of lysosomal cathepsin B compared with PD group (399.00%±35.54% vs. 305.90%±24.87%, P<0.05). Conclusion:The α-Syn aggregates incubated with plasma from PD and MSA patients have damage to mitochondrial and lysosome functions, especially those incubated with plasma from MSA patients.

Objective:To observe the effect of α-synuclein (α-Syn) aggregates incubated with plasma from patients with Parkinson's disease (PD) and multiple system atrophy (MSA) on mitochondrial and lysosomal functions, and further clarify the role of α-Syn in pathological mechanism of PD and MSA.Methods:Human neuroblastoma cells (SH-SY5Y) were treated with 10 μg/mL α-Syn aggregates incubated with phosphate buffered solution (PBS), and plasma from healthy controls (HCs), PD patients, and MSA patients, respectively; and the untreated SH-SY5Y cells were used as control group. Mito-Tracker Red CMXRos fluorescent staining was used to detect the mitochondrial membrane potential, Western blotting was used to detect the cytochrome C (Cyt C) expression in the mitochondria and cytoplasm, and adenosine triphosphate (ATP) test kit was used to detect the intracellular ATP level. In addition, the lysosomal associated membrane protein-1 (LAMP1) expression was detected by Western blotting, and cathepsin B activity was detected by Magic Red fluorescent staining.Results:(1) Effects of different α-Syn aggregates on mitochondrial function damage: compared with the control group, the PBS, HC, PD and MSA groups had significantly decreased relative fluorescent intensity (Mito-Tracker Red CMXRos staining) in the SH-SY5Y intracellular mitochondria ( P<0.05); the PD group and MSA group had significantly decreased relative fluorescent intensity compared with PBS group and HC group ( P<0.05); the MSA group had significantly decreased relative fluorescent intensity compared with the PD group (41.27%±5.97% vs. 60.05%±4.24%, P<0.05). Compared with the control group, the HC, PD and MSA groups had significantly decreased mitochondrial Cyt C protein expression, while the PBS, HC, PD and MSA groups had significantly increased cytoplasmic Cyt C protein expression ( P<0.05); the PD group and MSA group had significantly decreased mitochondrial Cyt C protein expression compared with the PBS group and HC group ( P<0.05); the MSA group had significantly increased cytoplasmic Cyt C protein expression compared with the PBS group ( P<0.05); the MSA group had significantly decreased mitochondrial Cyt C protein expression (51.50%±4.22%) and increased cytoplasmic Cyt C protein expression (199.40%±6.73%) compared with the PD group (65.52%±2.18% and 174.00%±16.18%, P<0.05). Compared with the control group, the PBS group, HC group, PD group and MSA group had significantly decreased ATP level ( P<0.05); the PD group and MSA group had significantly decreased ATP level compared with the PBS group and HC group ( P<0.05); the MSA group had significantly decreased ATP level (1.81±0.13 nmol/mg) compared with PD group (2.96±0.29 nmol/mg, P<0.05). (2) Effects of different α-Syn aggregates on lysosomal functions: compared with the control group, the PD group and MSA group had significantly decreased LAMP1 protein expression ( P<0.05); the MSA group had significantly decreased LAMP1 protein expression (60.74%±7.94%) compared with the PBS group, HC group, and PD group (79.70%±4.34%, P<0.05). Compared with the control group, the PBS, HC, PD and MSA groups had significantly enhanced relative fluorescent intensity of lysosomal cathepsin B ( P<0.05); the PD group and MSA group had significantly enhanced relative fluorescent intensity of lysosomal cathepsin B compared with PBS group and HC group ( P<0.05); the MSA group had significantly increased relative fluorescent intensity of lysosomal cathepsin B compared with PD group (399.00%±35.54% vs. 305.90%±24.87%, P<0.05). Conclusion:The α-Syn aggregates incubated with plasma from PD and MSA patients have damage to mitochondrial and lysosome functions, especially those incubated with plasma from MSA patients.

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.

Objective:To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice.Methods:A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode.Results:Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD ( P<0.05). Logistic regression analysis showed that visualization of pancreatic duct ( OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation ( OR=0.14), pancreatic atrophy ( OR=0.12) and external drainage ( OR=0.11) were protective factors for pancreatitis. Conclusion:In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.

Objective:To investigate the status of post-traumatic growth and its afffecting factors in middle-aged and young patients with type 2 diabetes, in order to carry out clinical intervention for reference.Methods:A general data questionnaire, Posttraumatic Growth Inventory, Perceived Social Support Scale, and Connor-Davidson Resilience Scale were used to survey 222 middle-aged and young patients with type 2 diabetes hospitalized from December 2020 to March 2021 in Shandong First Medical University Affiliated Center Hospital, Shandong Provincial Qianfoshan Hospital, Liaocheng People′s Hospital.Results:The total score of Posttraumatic Growth Inventory, Perceived Social Support Scale, and Connor-Davidson Resilience Scale was (45.20 ± 12.90), (42.73 ± 10.16),(51.41 ± 10.60) points in middle-aged and young patients with type 2 diabetes. Regression showed that treatment mode, medical payment mode, social support, and psychological resilience were the main influencing factors of post-traumatic growth levels in middle-aged and young patients with type 2 diabetes ( P<0.05), which could explain 42.3% of the variation. Conclusions:Middle-aged and young patients with type 2 diabetes have grown at low level. Medical staff should concentrate on the positive psychology of patients and improve their level of social support and resilience to promote the production of post-traumatic growth.

Objective To establish the pushing transmission model of tendon-sheath system (TSS) for endoscopic flexible instrument, and study the key influencing factors of transmission efficiency. Methods The force and displacement transmission models of TSS in pushing configuration were built and simulated. The tendon-sheath transmission testing platform was designed to validate the model. The influencing factors, such as transmission velocity, tendon-sheath diameter ratio, curvature radius, were explored using this setup. Results There were obvious nonlinear phenomenon in force and displacement transmission. The model simulation results accorded quite well with the experiment results. Transmission velocity, tendon-sheath diameter ratio, curvature radius all had great effects on pushing force transmission of endoscopic flexible instrument, while they had a smaller effect on displacement transmission. Conclusions The proposed model can be used for calculating pushing force transmission of tendon-sheath system for endoscopic flexible instrument, so as to provide the doctors with force feedback at the tip of the end effector, and ensure the safe operation and improve the surgical effects. For better design and control of endoscopic flexible instrument, the transmission velocity, tendon-sheath diameter ratio, curvature radius must be comprehensively considered.

Objective The ileum of porcine intestines with radiofrequency (RF) energy was fused through a novel linkage-type pressure controlled electrode, so as to verify feasibility and security of intestinal reconstruction in the RF energy tissue fusion technology. Methods Fresh porcine intestines were fixed on negative electrode in the order of ‘mucosa-serosa’, and then different compressive pressures （497，796，995，1 194，1 492 kPa）and RF energy were applied to the tissues through positive electrode of pressure cone to complete intestinal anastomosis. Biomechanical properties of the fused area were studied by tensile strength and bursting pressure test, and the thermal diffusion and tissue microstructure also studied. ResultsThe anastomotic tensile strength and bursting pressure could reach （8.73±1.11） N and （8.29±0.41） kPa, respectively, when the energy output power, pressure and welding time were 160 W, 995 kPa and 13 s, respectively, and an intact microstructure with little free collagen in the fused area could be observed. Conclusions The technology of RF energy-based tissue fusion could accomplish fast and stable intestinal tract reconstruction, showing great potential in clinical application. It is of great significance to shorten the operation time, simplify the operation process and improve the operation quality.