ObjectiveTo evaluate the pregnancy outcomes of assisted reproductive technology （ART） in women with a history of thyroid cancer who retained fertility intentions after completing cancer treatment. MethodsA retrospective analysis was performed on 61 patients with a history of thyroid cancer who underwent in vitro fertilization/intracytoplasmic sperm microinjection and embryo transfer （IVF/ICSI-ET）. These patients were included as the case group. A total of 122 non-cancer patients who received ART during the same period were selected as the control group using 1∶2 matching based on age and oocyte retrieval time. Baseline characteristics， outcomes of the first ART cycle， and cumulative pregnancy outcomes were compared between the two groups. ResultsThere was no significant difference in the basic data， the total amount of gonadotropin （Gn） and the days of use between the case group and the control group （P>0.05）. However， the case group had significantly fewer retrieved oocytes， mature oocytes （MII）， lower fertilization and cleavage rates， and fewer transferable and high-quality embryos， as well as fewer embryos transferred during the first cycle （P < 0.05）. However， there was no significant difference in the rate of first embryo implantation and first clinical pregnancy between the two groups （P>0.05）. In the analysis of cumulative outcomes， the two groups did not show statistically significant differences in the cumulative pregnancy rate， clinical pregnancy rate per transfer cycle， the number of oocyte retrieval cycles required per live birth， the number of embryo transfer cycles required per live birth， and the number of embryos used for each live birth （P>0.05）. However， the cumulative live birth rate was significantly lower in the case group compared to the control group （P=0.005）. ConclusionAfter treatment for thyroid cancer， when ART is used to help pregnant women， the pregnancy outcome is comparable to that of women without tumors. Individualized reproductive management and timely fertility preservation strategies are recommended to optimize reproductive outcomes in this population.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

Symptom and syndrome efficacy evaluation scales are indispensable tools for clinical efficacy assessment in traditional Chinese medicine （TCM）， and hold significant value at all stages of new drug research development for spleen and stomach diseases. These scales can provide scientific basis for clinical positioning， efficacy evaluation， and expansion of indications of new drugs. By analyzing the current hotspots and difficulties in research， this study aims to explore the important significance of these scales in the development of new drugs for spleen and stomach diseases， summarize the domestic research progress， and conduct comparative analyses with international studies. Future development trends are also discussed in order to promote the application of symptom and syndrome efficacy evaluation scales in the development of new drugs for spleen and stomach diseases and to advance the moder-nization process of TCM.

Receptor tyrosine kinases (RTKs) are a class of transmembrane cell surface enzyme-linked receptors that play essential roles in various cellular life processes under normal physiological conditions. Dysregulation of RTKs and their signaling pathways is closely associated with multiple human diseases, including cancer. RON is a member of the RTK family. When RON is abnormally expressed, it can actively drive the proliferation, metastasis, and epithelial-mesenchymal transition of cancer cells through complex downstream signal transduction pathways, thereby contributing to the occurrence and subsequent development process of various types of cancers. Consequently, RON is regarded as a potent target for cancer targeted therapy. In recent years, as RTKs have gradually become popular candidate targets for antibody-drug conjugates (ADCs), a variety of ADCs targeting RON have been successfully developed and studied. To highlight the therapeutic potential of anti-RON ADCs in cancer treatment and to provide a foundation for further development and clinical research of them, this article summarized the selected components and construction strategies of existing anti-RON ADCs, and systematically reviewed their in vitro and in vivo anticancer efficacy, as well as their pharmacological and toxicological characteristics. Anti-RON ADCs demonstrated favorable stability both in vitro and in vivo. In cellular models, anti-RON ADCs carrying different payloads all exhibited potent cytotoxic effects. In animal models, anti-RON ADCs have convincingly demonstrated significant anti-cancer activity, with stable pharmacological properties and manageable toxicity at therapeutic doses. Anti-RON ADCs have a number of distinct therapeutic advantages. Compared with ADCs targeting other RTKs, anti-RON ADCs have unique effects in regulating the immune microenvironment and can potentially provide additional therapeutic options for overcoming drug resistance. Compared with RON antibodies and small molecule inhibitors, anti-RON ADCs do not rely on the RON signaling pathways, thereby significantly enhancing therapeutic efficacy. Moreover, anti-RON ADCs show therapeutic potential for targeting RON variants. In summary, the results of basic researches indicated that anti-RON ADCs have favorable anti-cancer effects and show promising clinical translation prospects. In addition, this article analyzed the current limitations of anti-RON ADCs and emphatically discussed their future development directions. The payloads of the existing anti-RON ADCs are relatively limited, and the drug-to-antibody ratio (DAR) of each ADC is not uniform. There also remains considerable room for improvement in terms of endocytosis efficiency and drug combination strategies. Therefore, the development of the next-generation anti-RON ADCs should focus on the diversification of the payloads, and explore new types of ADCs, dual-load ADCs, etc. Additionally, the structure of antibodies or ADCs could be optimized to enhance the endocytosis efficiency and progressively overcome current limitations. At present, anti-RON ADCs are limited to basic research, and the current research outcomes and observations indicated their potential for clinical application. Therefore, the clinical translation of anti-RON ADCs will be an important objective for future development. To this end, it is necessary to carefully devise a rational clinical translation pathway for anti-RON ADCs, and comprehensively evaluate the potential challenges that may arise during the implementation, so as to accelerate the initiation of clinical trials. Ultimately, clinical application of anti-RON ADCs will be realized, providing more treatment options for cancer patients.

Objective The aim was to evaluate the effects of efforts directed toward controlling Oncomelania hupensis snails on small environmental modification projects in Anqing City to provide a reference for comprehensively controlling O. hupensis in hilly areas where schistosomiasis is endemic. Methods Field and retrospective surveys were conducted to collect data using questionnaires. The data from 35 questionnaires on small-scale environmental modification projects in Anqing City and the effects of snail obtained from monitoring forms were sorted. The data were descriptively analyzed using basic information on environmental modifications and investment costs. The Wilcoxon signed-rank test was used to compare snail status before and after environmental interventions. The Friedman test was applied to evaluate the changes in snail populations in the years after environmental intervention. Non-parametric independent sample tests were adopted to compare differences in the effects of different environmental interventions, environmental characteristics, and between project and control areas. Results A total of 35 environments altered from 2017 to 2023, including the creation of 29 ditches,1 dry land, and 5 pond-weirs. The main environmental interventions included hardening of ditches and pond-weirs as well as tilling with intercropping. The average investment costs of mortared rubble masonry hardening and tilling with intercropping were the highest(147.10 yuan/m2)and lowest(4.62 yuan/m2), respectively. The pre-intervention snail-infested area was 78 900 m2, which decreased to 18 100 m2, a decrease of 77.06%. After environmental intervention, the density and rate of living snails significantly decreased on frames with snails(P<0.001). In ditch environments, the smoothness of the ditch walls and the presence of snails in the upper reaches did not significantly decrease the living snail density; however, the presence of cracks on the inner side of the ditches significantly impacted the decline in the rate(P<0.001). No significant difference was found in the rates at which the living snail density or snail frame occurrence decreased among different environmental modification method. The effects of brick masonry, concrete, and mortared rubble masonry on snail control were significantly stronger than those of chemical snail control(P<0.01), whereas no significant difference was found in the decline in these two rates between project areas using other modification method and control areas using chemical snail control. Conclusions Schistosomiasis-prevention-oriented environmental interventions effectively eliminate snails from hilly snail-infested areas. Cost-effective modification method should be selected based on the environmental type, and post-modification monitoring and maintenance must be strengthened to further increase snail control effectiveness.

BackgroundObstructive sleep apnea （OSA） represents a prevalent sleep disordered breathing condition characterized by complex pathophysiology. The arousal threshold （ArTH）， a core non-anatomical contributor to OSA pathogenesis， is intimately tied to the disease severity and clinical phenotypes. To date， research regarding factors associated with ArTH has yielded inconsistent findings， and ArTH profiles and disparities across populations with different genetic backgrounds are not fully elucidated. ObjectiveTo explore the differences of ArTH in OSA patients with different genetic backgrounds and analyze the key factors affecting ArTH， thereby providing evidence for understanding OSA pathophysiology and formulating targeted treatment regimens. MethodsA total of 285 patients who met the diagnostic criteria for OSA， as defined by the Multidisciplinary Diagnosis and Treatment Guidelines for Adult Obstructive Sleep Apnea， were retrospectively enrolled in this study. All participants underwent overnight polysomnography （PSG） at the Sleep Medicine Center of Inner Mongolia Mental Health Center from December 2022 to May 2024. Based on the study design， the cohort was stratified into two distinct genetic background subgroups （group A and group B）. Demographic and clinical characteristics， the Epworth Sleepiness Scale （ESS） score， and overnight PSG data were collected. The apnea hypopnea index （AHI）， the lowest pulse oxygen saturation （LSpO₂）， and fraction of hypopneas （F_Hypopneas） were utilized as surrogate indicators to estimate ArTH in OSA patients. The influencing factors of low ArTH were tested by binary Logistic regression analysis. ResultsAmong the 285 OSA patients， there were 227 cases （79.65%） in group A and 58 cases （20.35%） in group B. Comparisons between the two genetic background subgroups revealed no statistically significant differences in the proportion of low ArTH， ESS score， PSG parameters， and the three markers for low ArTH （AHI<30 events/h， LSpO₂>82.5%， F_Hypopneas>58.3%） （P>0.05）. Binary Logistic regression analysis identified sex （OR=2.421， 95% CI： 1.070–5.478）， BMI （OR=0.847， 95% CI： 0.770–0.932）， N1 sleep duration （OR=0.974， 95% CI： 0.963–0.985）， and hypertension （OR=0.348， 95% CI： 0.143–0.848） as independent factors associated with low ArTH in the total cohort. Stratified analysis by genetic backgrounds revealed that sex（OR=3.799， 95% CI： 1.389–10.392）， BMI（OR=0.819， 95% CI：0.723–0.929）， and N1 sleep duration（OR=0.973， 95% CI： 0.961–0.986） were independent factors of low ArTH in group A. In contrast， only N1 sleep duration （OR=0.951， 95% CI： 0.911–0.993） remained a significant factor in group B. ConclusionArthur may have conservative characteristics in patients with OSA with different genetic backgrounds， but the pathophysiological mechanism of OSA may have population heterogeneity. ［Funded by Inner Mongolia Autonomous Region Natural Science Fundation Project （number， 2024QN08050）； Intra-institutional Scientific Research Project of Inner Mongolia Mental Health Center （number， 2022QNWN0010）］

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS. METHODS: A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0. RESULTS: Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode ( P = 0.001). CONCLUSION Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
Humans ; Female ; COVID-19/epidemiology* ; Retrospective Studies ; Adult ; Pregnancy ; Lower Urinary Tract Symptoms/virology* ; Postpartum Period ; Pregnancy Complications, Infectious/virology* ; China/epidemiology* ; Electromyography ; SARS-CoV-2/physiology* ; Pelvic Floor/physiopathology* ; Prevalence

BackgroundThe functional changes of the default mode network （DMN） are closely related to the onset of major depressive disorders. However， the relationship between the DMN subsystem （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and symptoms of first-episode major depressive disorder remains unclear. ObjectiveTo investigate abnormal functional connectivity between DMN subsystems and the whole brain in first-episode major depressive disorder patients during the resting-state， and to analyse the correlations between these functional connectivity patterns and clinical symptoms， so as to reveal the potential neural mechanisms from the perspective of DMN subsystem. MethodsFrom September 2020 to September 2023， a total of 64 first-episode outpatients and inpatients meeting the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Inner Mongolia Autonomous Region Mental Health Center as the study group. During the same period， 54 healthy volunteers matched for age， gender， and years of education were recruited from the community as the control group. Both groups were assessed using the Hamilton Depression Scale-24 item （HAMD-24）. Resting-state functional magnetic resonance images （rs-fMRI） of the two groups were acquired using a Siemens 3.0 T scanner， and differences in functional connectivity between DMN subsystems （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and the whole brain were compared. The functional connectivity values of brain regions with statistically significant differences between the two groups were extracted. Spearman's rank correlation coefficient analysis was used to investigate the correlation between these functional connectivity values and HAMD-24 scores of the study group. ResultsUltimately， 46 patients and 43 controls completed the study. Compared with the control group， the study group exhibited significantly stronger functional connectivity in the following pathways： between the right superior parietal lobule （core subsystem） and right cerebellar lobule VIII （t=3.954， P<0.05， GRF-corrected）， between the right lateral temporal cortex （dorsomedial prefrontal cortex subsystem） and right cerebellar lobule VIII， right and left hippocampi， right medial， and paracingulate gyrus （t=4.595， 4.208， 5.200， 4.038， P<0.05， GRF-corrected）， and between the temporoparietal junction （dorsomedial prefrontal cortex subsystem） and left lingual gyrus and right cerebellar lobule VIII （t=3.557， 4.274， P<0.05， GRF-corrected）. Conversely， weaker functional connectivity was observed between the right inferior frontal gyrus and left gyrus rectus （t=-3.824， P<0.05， GRF-corrected）. Furthermore， within the study group， the functional connectivity values between the right lateral temporal cortex and right hippocampus， as well as between the temporoparietal junction and right cerebellar lobule VIII， were both negatively correlated with the HAMD-24 cognitive impairment factor score （r=-0.306， -0.318， P<0.05）. ConclusionIncreased functional connectivity between the DMN （specifically its core and dorsomedial prefrontal cortex subsystems） and cerebellum， partial limbic system， and lingual gyrus may be associated with the neuropathology of first-episode major depressive disorder. Furthermore， alterations in functional connectivity between the dorsomedial prefrontal cortex subsystem and both the cerebellum and hippocampus in these patients may be related to cognitive function. ［Funded by 2019 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2019MS03038）； 2023 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2023MS08028）］