Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Objective:To investigate the longitudinal trajectories of symptom clusters in elderly patients with laparoscopic surgery for colon cancer, and explore the predictive factors for each trajectories subgroup.Methods:Using a longitudinal survey, elderly patients with laparoscopic surgery for colon cancer patients from Shanxi Bethune Hospital from January 2021 to January 2024 were collected by convenient sampling method. The Chinese Version of the MD Anderson Symptom Inventory Gastrointestinal Cancer Module was used to conduct follow-up surveys of the selected patients at 2 weeks, 1 month, 3 months and 6 months after surgery. The symptom cluster was extracted by exploratory factor analysis, and the latent category growth model was conducted to identify the trajectory subgroups of each symptom cluster, the predictive factors of each trajectory subgroup was analyzed by multiple Logistic regression analysis.Results:A total of 118 cases were concluded in the present study, there were 69 males and 49 females with an age of (74.85 ± 3.29) years old. There were 4 symptom clusters after surgery, which were named as energy deficit symptom cluster, digestive tract symptom cluster, sleep mental symptom cluster, and psychological fatigue symptom cluster, the variance contribution rates were respectively 62.486%, 71.209%, 73.937%, 63.476%. The results from latent class growth model showed that there were 3 trajectory subgroups in the symptom cluster: high level-slow decline group accounted for 33.0% (39/118), moderate level-stable decline group accounted for 39.0% (46/118), low level-rapid decline group accounted for 28.0% (33/118). College education or above tends to developed into low level-rapid decline group ( OR=0.365, 95% CI 0.083-0.603, P<0.05), while patients undergoing traditional laparoscopic surgery ( OR=3.679, 95% CI 1.297-4.432, P<0.05) and primary tumor stages of Ⅲ-Ⅳ were more likely to developed into high level-slow decline group ( OR=0.333, 95% CI 0.120-0.920, P<0.05). Conclusions:There are 4 symptom clusters in elderly patients with laparoscopic surgery for colon cancer, and the characteristics of postoperative symptom cluster changes demonstrate significant heterogeneity, medical staff should pay attention to the management of symptom clusters trajectory categories, dynamically adjust intervention plans to improve nursing quality.

ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Objective To evaluate the efficacy of human papillomavirus E6/E7(HPV E6/E7)mRNA combined with colposcopy in screening cervical cancer and precancerous lesions.Methods A total of 480 patients with suspected cervical precancerous lesions in the hospital from July 2022 to De-cember 2024 were retrospectively selected as research objects.All the patients underwent HPV E6/E7 mRNA testing,colposcopy,and pathological examination.Taking the pathological examination results as the diagnostic golden standard,the diagnostic values of HPV E6/E7 mRNA and colposcopy alone as well as their combination were analyzed.Results The pathological examination results of 480 pa-tients showed that there were 192 negative cases,including 1 case of normal cervix and 191 cases of benign lesions;there were 288 positive cases,including 133 cases of low-grade squamous intraepithe-lial lesions(LSIL),110 cases of high-grade squamousintraepithelial lesions(HSIL),and 45 cases of cervical squamous cell carcinoma(SCC).The colposcopy results showed 211 true-positive cases and 138 true-negative cases;the HPV E6/E7 mRNA test results showed 199 true-positive cases and 137 true-negative cases;the combined test results showed 239 true-positive cases and 174 true-negative cases.The sensitivity(95.22％),specificity(75.98％),accuracy(86.04％),positive predic-tive value(81.29％),and negative predictive value(93.55％)of the combined test were signifi-cantly higher than those of each individual test(P＜0.001).Moreover,the consistency between the combined test and pathological results(Kappa=0.718,P＜0.001)was also significantly high-er than that of each individual test.Conclusion Compared with HPV E6/E7 mRNA or colposcopy alone,the combined test has higher clinical application value in screening of cervical precancerous lesions and cervical cancer,shows stronger consistency with pathological results,and is of great sig-nificance for the early differential diagnosis of cervical precancerous lesions and cervical cancer.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Due to its high immunogenicity and tumor specificity, tumor neoantigen has emerged as an important target for tumor immunotherapy. The capacity of microorganisms to modulate the immune system, thereby activating neoantigen-specific T cells and utilizing the phenomenon of molecular mimicry, underscores their potential for broad application in the development of cancer vaccines. In this review, the mechanisms of action of microorganisms in neoantigen immunotherapy were examined, and the applications of bacteria and their derivatives, viral vectors, and fungal vectors in delivering tumor neoantigens were summarized. The significance of microorganisms in tumor neoantigen immunotherapy was underscored, and a reference for future research and clinical application was provided.

Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95％CI 0.97-0.99,P＜0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P＜0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P＞0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.

At present, liver transplantation is the most effective method for the treatment of various end-stage liver diseases, and electronic health technology is a new medical service model, which can be used as an efficient and cost-effective alternative to the health management of liver transplant recipients. This paper summarizes the application of electronic health technology in postoperative health management of liver transplant recipients, including applications, robots, video conferencing, tablet computers, text messages, telephones and wearable devices, etc., summarizes the implementation effect of electronic health technology in health management of liver transplant recipients, and analyzes the limitations of research and application at the present stage. In order to provide basis and reference for Chinese medical staff to carry out electronic health technology in the health management of liver transplant recipients.