OBJECTIVE Aimed to investigate the impact of comorbid asthma on chronic rhinosinusitis with nasal polyps(CRSwNP)and identify key proteins and signaling pathways.METHODS Proteomic methods were employed to analyze differentially expressed proteins(DEPs)in nasal lavage fluid(NLF)from control,CRSwNP,and CRSwNP with asthma groups.DIA quantitative analysis technology was used to assess the gradient changes of DEPs among the three groups to determine key proteins affected by comorbid asthma in CRSwNP.RESULTS Compared to the control group,1 377 and 1 006 DEPs were identified in the CRSwNP and CRSwNP with asthma groups,respectively.Peroxiredoxin-5(PRDX5),Ran-Binding Protein 1(RanBP1)(upregulated),and Keratin 9(KRT9)(downregulated)were identified as key proteins affecting CRSwNP with asthma.CONCLUSION Comorbid asthma may promote the occurrence and development of nasal polyps through specific key proteins and signaling pathways,providing new molecular insights into the interaction between CRSwNP and asthma.

Objective:To explore the clinical application value of optical navigation system（ONS）-guided sacral neuromodulation（SNM）electrode implantation for precise puncture.Methods:?This study was a randomized，controlled trial. Patients who underwent SNM electrode implantation at the Gongli Hospital，Pudong New Area，Shanghai，from February 2024 to March 2025 were included. Inclusion criteria：aged 18?80 years，meeting the indications recommended by the Chinese expert consensus on the clinical application of sacral neuromodulation or expanded applications，and having completed pelvic CT and MRI examinations to ensure image quality for navigation system use. Exclusion criteria：progressive neurological diseases，severe urinary tract infections，urinary tract obstruction，or other conditions that may affect surgical outcomes and safety. Patients were randomly divided into two groups using a random number table and a single-blind design was implemented. The two groups underwent different puncture guidance methods in the stage Ⅰ surgery，but other treatments and follow-up measures were consistent.The experimental group used ONS-guided puncture with preoperative pelvic CT and MRI scans for multimodal image fusion and 3D reconstruction and software-based puncture path planning for real-time intraoperative guidance. The control group used X-ray-guided cross-positioning，determining the S3 sacral foramen for puncture based on anatomical landmarks with a metal positioning ruler under fluoroscopy. The puncture path was planned using software to achieve real-time intraoperative guidance. Intraoperative indicators（number of punctures，puncture time，electrode contact points，minimum effective voltage，X-ray fluoroscopy time，radiation dose，total surgical time）and postoperative outcomes（complications，pain scores，stage Ⅱ permanent implantation rates）were compared between the two groups to assess the advantages and feasibility of ONS-guided sacral nerve electrode implantation.Results:?A total of 35 patients were included in each group. The experimental group had fewer intraoperative puncture attempts［2.0（2.0，3.0）vs. 5.0（4.0，7.0）］and shorter puncture procedure time［7.5（6.0，10.0）min vs. 14.0（12.0，18.0）min］，indicating more accurate and efficient ONS-guided puncture. There was no statistical difference in the number of electrode contact points between the two groups［3.0（3.0，4.0）vs. 3.0（3.5，3.8）， P = 0.374］，but the experimental group had a lower effective voltage［1.8（1.8，2.5）V vs. 2.5（1.8，3.0）V］and shorter stimulator adjustment time［10.0（8.0，12.0）min vs. 16.0（13.0，20.0）min］. The experimental group had shorter intraoperative X-ray fluoroscopy time［1.6（1.1，2.2）min vs. 4.6（3.8，6.0）min］，lower radiation dose［165.8（107.6，205.3）mGy vs. 427.4（325.1，636.5）mGy］，shorter total surgical time［52.0（49.0，57.8）min vs. 68.0（62.0，74.0）min］，less intraoperative blood loss［4.0（4.0，5.0）ml vs. 6.0（5.0，7.0）ml］，and a lower proportion of patients requiring supplemental local anesthesia［14.3%（5/35）vs. 40.0%（14/35）］. The postoperative wound infection rates were not statistically different between the two groups［0 vs. 2.9%（1/35）， P = 1.000］，but the experimental group had significantly lower pain scores on postoperative day 1［（1.9 ± 1.1）vs.（3.2 ± 1.4）］and a higher stage Ⅱ permanent implantation rate［85.7%（30/35）vs. 65.7%（23/35）］，with statistically significant differences（ P < 0.05）. Conclusions:?ONS-guided SNM electrode implantation reduces the number of puncture attempts，surgical time，and X-ray radiation，effectively lowers the effective voltage，and increases the stage Ⅱ permanent implantation rate.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Objective: To investigate the clinical efficacy and safety of pudendal nerve modulation (PNM) in the treatment of female pudendal neuralgia (PN)，so as to promote the clinical application of this technique. Methods: A retrospective analysis was conducted on 20 female PN patients who failed conservative treatment at Gongli Hospital during Nov.2020 and Oct.2023.All patients underwent simultaneous PNM and sacral nerve modulation (SNM) with the assistance of 3D printing navigation.Dual-stage test electrodes for PNM and SNM were implanted，followed by alternate therapeutic trial for each modality.Secondary conversion rates and longitudinal outcomes，including visual analogue score (VAS)，patient health questionnaire-9 (PHQ-9)，and quality of life (QoL) scores were compared preoperatively，post-stage Ⅰ，and at 3，6，and 12 months post-stage Ⅱ. Results: All operations were successful.After the trial phase，the secondary conversion rate for PNM was significantly higher than that for SNM; 16 patients (16/20，80%) chose the second-phase PNM implantation surgery，3 (3/20，15%) chose second-phase SNM implantation，and 1 (1/20，5%) had electrodes removed due to ineffective results from both trials.Further assessment revealed that the improvements in VAS，PHQ-9，and QoL scores for PNM patients were significantly better than those for SNM patients after the first phase of surgery and at 3，6 and 12 months after the second-phase conversion (P<0.05).No complications such as electrode migration or infection were observed during the follow-up of 12-15 months. Conclusion: PNM provides more effective relief of pain symptoms and improvements in depressive states for female PN patients compared to SNM.With the assistance of 3D printing navigation，the operation is simple and safe，and offers stable therapeutic effects.It is worthy of clinical promotion and application.

Objective:To explore influence of Treg/Th17 balance on relative risk of acute exacerbation in patients with chronic obstructive pulmonary disease(COPD).Methods:A prospective cohort study was used to select 246 patients with COPD treated in emergency department of Beidaihe Hospital from January 2021 to January 2023,who were divided into acute aggravation group(113 cases)and stable group(133 cases)according to GOLD guidelines.Clinical indicators and lung function levels of two groups were compared,and risk variables of acute exacerbation in COPD patients were analyzed by Logistic multivariate regression.Restricted cubic spline model was used to analyze correlation between Treg/Th17 level and acute exacerbation in COPD patients.A line graph model was constructed and validation based on risk factors.The model was stratified according to risk score of column graph by X-tile software,and clinical application value of model was further discussed.Results:①Th17,IL-17,IL-22,C-reactive protein change rate(ΔCRP),procalcitonin change rate(ΔPCT)and TGF-β1 levels in acute aggravation group were significantly higher than stable group,Treg and Treg/Th17 levels were lower than stable group(P<0.05);②Multivariate Logistic regression analysis found that Treg≤9.06%,Th17≥2.23%,Treg/Th17≤5.27,ΔPCT≥0.845,ΔCRP≥0.554,IL-17≥37.55 ng/L,IL-22≥14.14 ng/L,TGF-β1≥840.56 ng/L were risk factors for COPD patients with acute exacerbation(P<0.05);③Restricted cubic spline model analysis showed that Treg/Th17 level was correlated with COPD acute exacerbation(χ2=7.214,P=0.001),and there was a linear dose-response relationship(χ2=3.542,P=0.112);④A line graph prediction model was constructed based on the above eight risk factors and evaluation results showed that C-index before and after verification were 0.864 and 0.831,respectively;AUC before and after validation were 0.856 and 0.832,respectively,and correction curve before and after validation fitted well with ideal curve.Clinical decision curve showed that when threshold probability was 0.01～0.91,higher net benefit could be obtained by this model;⑤Risk stratification showed that inci-dence of acute exacerbation in high risk group was significantly higher than medium and low risk groups(χ2=6.056,P=0.013).Con-clusion:Monitoring changes in peripheral blood Treg/Th17 cell balance provides a high reference value for acute exacerbations in patients with COPD.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To explore influence of Treg/Th17 balance on relative risk of acute exacerbation in patients with chronic obstructive pulmonary disease(COPD).Methods:A prospective cohort study was used to select 246 patients with COPD treated in emergency department of Beidaihe Hospital from January 2021 to January 2023,who were divided into acute aggravation group(113 cases)and stable group(133 cases)according to GOLD guidelines.Clinical indicators and lung function levels of two groups were compared,and risk variables of acute exacerbation in COPD patients were analyzed by Logistic multivariate regression.Restricted cubic spline model was used to analyze correlation between Treg/Th17 level and acute exacerbation in COPD patients.A line graph model was constructed and validation based on risk factors.The model was stratified according to risk score of column graph by X-tile software,and clinical application value of model was further discussed.Results:①Th17,IL-17,IL-22,C-reactive protein change rate(ΔCRP),procalcitonin change rate(ΔPCT)and TGF-β1 levels in acute aggravation group were significantly higher than stable group,Treg and Treg/Th17 levels were lower than stable group(P<0.05);②Multivariate Logistic regression analysis found that Treg≤9.06%,Th17≥2.23%,Treg/Th17≤5.27,ΔPCT≥0.845,ΔCRP≥0.554,IL-17≥37.55 ng/L,IL-22≥14.14 ng/L,TGF-β1≥840.56 ng/L were risk factors for COPD patients with acute exacerbation(P<0.05);③Restricted cubic spline model analysis showed that Treg/Th17 level was correlated with COPD acute exacerbation(χ2=7.214,P=0.001),and there was a linear dose-response relationship(χ2=3.542,P=0.112);④A line graph prediction model was constructed based on the above eight risk factors and evaluation results showed that C-index before and after verification were 0.864 and 0.831,respectively;AUC before and after validation were 0.856 and 0.832,respectively,and correction curve before and after validation fitted well with ideal curve.Clinical decision curve showed that when threshold probability was 0.01～0.91,higher net benefit could be obtained by this model;⑤Risk stratification showed that inci-dence of acute exacerbation in high risk group was significantly higher than medium and low risk groups(χ2=6.056,P=0.013).Con-clusion:Monitoring changes in peripheral blood Treg/Th17 cell balance provides a high reference value for acute exacerbations in patients with COPD.

Objective:To explore the clinical application value of optical navigation system（ONS）-guided sacral neuromodulation（SNM）electrode implantation for precise puncture.Methods:?This study was a randomized，controlled trial. Patients who underwent SNM electrode implantation at the Gongli Hospital，Pudong New Area，Shanghai，from February 2024 to March 2025 were included. Inclusion criteria：aged 18?80 years，meeting the indications recommended by the Chinese expert consensus on the clinical application of sacral neuromodulation or expanded applications，and having completed pelvic CT and MRI examinations to ensure image quality for navigation system use. Exclusion criteria：progressive neurological diseases，severe urinary tract infections，urinary tract obstruction，or other conditions that may affect surgical outcomes and safety. Patients were randomly divided into two groups using a random number table and a single-blind design was implemented. The two groups underwent different puncture guidance methods in the stage Ⅰ surgery，but other treatments and follow-up measures were consistent.The experimental group used ONS-guided puncture with preoperative pelvic CT and MRI scans for multimodal image fusion and 3D reconstruction and software-based puncture path planning for real-time intraoperative guidance. The control group used X-ray-guided cross-positioning，determining the S3 sacral foramen for puncture based on anatomical landmarks with a metal positioning ruler under fluoroscopy. The puncture path was planned using software to achieve real-time intraoperative guidance. Intraoperative indicators（number of punctures，puncture time，electrode contact points，minimum effective voltage，X-ray fluoroscopy time，radiation dose，total surgical time）and postoperative outcomes（complications，pain scores，stage Ⅱ permanent implantation rates）were compared between the two groups to assess the advantages and feasibility of ONS-guided sacral nerve electrode implantation.Results:?A total of 35 patients were included in each group. The experimental group had fewer intraoperative puncture attempts［2.0（2.0，3.0）vs. 5.0（4.0，7.0）］and shorter puncture procedure time［7.5（6.0，10.0）min vs. 14.0（12.0，18.0）min］，indicating more accurate and efficient ONS-guided puncture. There was no statistical difference in the number of electrode contact points between the two groups［3.0（3.0，4.0）vs. 3.0（3.5，3.8）， P = 0.374］，but the experimental group had a lower effective voltage［1.8（1.8，2.5）V vs. 2.5（1.8，3.0）V］and shorter stimulator adjustment time［10.0（8.0，12.0）min vs. 16.0（13.0，20.0）min］. The experimental group had shorter intraoperative X-ray fluoroscopy time［1.6（1.1，2.2）min vs. 4.6（3.8，6.0）min］，lower radiation dose［165.8（107.6，205.3）mGy vs. 427.4（325.1，636.5）mGy］，shorter total surgical time［52.0（49.0，57.8）min vs. 68.0（62.0，74.0）min］，less intraoperative blood loss［4.0（4.0，5.0）ml vs. 6.0（5.0，7.0）ml］，and a lower proportion of patients requiring supplemental local anesthesia［14.3%（5/35）vs. 40.0%（14/35）］. The postoperative wound infection rates were not statistically different between the two groups［0 vs. 2.9%（1/35）， P = 1.000］，but the experimental group had significantly lower pain scores on postoperative day 1［（1.9 ± 1.1）vs.（3.2 ± 1.4）］and a higher stage Ⅱ permanent implantation rate［85.7%（30/35）vs. 65.7%（23/35）］，with statistically significant differences（ P < 0.05）. Conclusions:?ONS-guided SNM electrode implantation reduces the number of puncture attempts，surgical time，and X-ray radiation，effectively lowers the effective voltage，and increases the stage Ⅱ permanent implantation rate.