Functional dyspepsia （FD） is a prioritized disease category where traditional Chinese medicine （TCM） demonstrates distinct therapeutic advantages. The current western medicine treatment for FD is mainly based on proton pump inhibitors and prokinetic agents， with digestive enzymes， probiotics and antidepressants serving as adjuvant medication， yet such therapies still have certain limitations. TCM treatment for FD includes oral administration of Chinese herbal formulas and Chinese patent medicines， as well as external TCM therapies such as acupuncture and moxibustion， acupoint application， hot medicinal compress therapy， rubbing with ointment， medicinal iontophoresis， auricular acupoint therapy and tui na （Chinese medical massage）. The combined treatment of FD with integrated TCM and western medicine can significantly improve clinical effectiveness and reduce adverse reactions. The common mechanisms underlying the therapeutic effects of both TCM and western medicine revolve around the core pathological processes of FD， mainly focusing on restoring gastrointestinal motility， regulating the levels of brain-gut peptides， modulating intestinal microecology， and ameliorating inflammatory status. The differential mechanisms lie in the precise targeting feature of western medicine versus the holistic-regulating and multi-target characteristics of TCM， and the two approaches exert a synergistic effect to enhance efficacy. This paper proposes to leverage the advantages of TCM in holistic regulation and the strengths of western medicine in targeted treatment， so as to provide personalized and comprehensive treatment regimens for FD patients.

Irritable bowel syndrome （IBS） is a functional bowel disorder characterized primarily by abdominal pain and altered defecation habits. In recent years， traditional Chinese medicine （TCM） has made progress in multiple aspects of IBS research and treatment， including syndrome distribution， development of TCM formulas， clinical efficacy evaluation， external therapies， and psychosocial regulation. However， it still faces challenges such as over-reliance on symptomatic manifestations rather than biomarkers for diagnostic criteria， and the lack of high-quality evidence-based data supporting the efficacy of TCM formulas in treating IBS. This paper proposed that TCM diagnosis and treatment of IBS should adhere to the strategy of integrating the holistic concept with syndrome differentiation and treatment， combining TCM external therapies such as acupuncture， moxibustion and acupoint application）， and emphasizing individualized diagnosis and treatment for psychosomatic abnormalities. Future research should integrate multi-omics technologies， artificial intelligence and other methods to deepen the understanding of the pathogenesis of IBS and the mechanisms of TCM formulas， so as to promote the standardization and internationalization of TCM in the diagnosis and treatment of IBS.

Brain science research involves technological applications such as bioengineering， information technology， artificial intelligence （AI）， and brain-computer interfaces， making it a focal area where advanced technologies and ethical issues converge. Currently， brain projects in multiple countries have entered their second-phase project processes and begun to reflect on the ethical challenges that emerged during the initial research phase. By sorting out and analyzing the coping strategies for ethical issues adopted by major international organizations related to brain science and countries that have launched brain projects， this paper pointed out the problems existing in brain science research， such as information security and data rights， the boundaries of technical power， the balance of stakeholders， the reductionist paradigm and the trend of technological dehumanization， as well as the inadequacy and practicality of ethical principles. It also analyzed the enlightenment of the global brain project’s ethical governance practices for China’s brain science ethical research， namely， avoiding overly optimistic deconstruction of the human brain through biological reductionism and preventing technocratic impulses to replace or manipulate the rich psychological experiences of human beings with AI or brain-computer interfaces. This paper proposed recommendations for developing neuroethics， advocating for constructing a technology development path enriched with humanistic care under the framework of scientific and technological ethics while strengthening foundational research in neuroethics.

In recent years, the incidence of multiple primary lung cancer (MPLC) has been increasing, and it cannot be ignored in clinical practice. The treatment of MPLC is still controversial, but surgical treatment is recognized as the most important treatment. However, current studies have shown that the treatment of MPLC needs to develop multimodal treatment according to different patients. This review summarizes multiple treatment method for MPLC, including surgery, ablation, chemotherapy, radiotherapy, targeted therapy, and immunotherapy in order to enhance understanding of MPLC treatment.
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Humans ; Lung Neoplasms/surgery* ; Immunotherapy ; Combined Modality Therapy

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To analyze the hearing screening effect of newborns in Ningbo City and provide references for further promoting neonatal hearing screening.Methods Otoacoustic emission was applied to screen the hearing of 835 323 newborns in Ningbo City from 2013 to 2023.Those who failed the initial screening were re-checked within 30 to 42 days.Those who failed the re-checking were referred to the municipal hearing diagnosis center for audiological diagnosis.The diagnosis data were enrolled,analyzed,and reported.Results Among a total of 835 323 newborns,828 043 of them actually underwent hearing screening,with an initial screening rate of 99.13％,761 369 newborns passed the initial screening with an initial screening pass rate of 91.95％.64 580 newborns were re-checked with a re-checking rate of 96.86％.There were 10 487 newborns re-checking failures,with a re-checking failure rate of 16.24％.A total of 10 164 cases were diagnosed with hearing loss,with a diagnosis rate of 96.92％.There were 323 cases of loss to follow-up with a loss to follow-up rate of 3.08％.A total of 1582 cases of hearing loss were diagnosed,with an incidence of hearing abnormalities of 1.91‰.Among the 1582 confirmed cases of hearing abnormalities,the diagnosis rate within 3 months was 12.01％,within 6 months was 57.90％,and within 12 months was 90.52％.The average diagnosed age was(7.21±6.55)months,while the median diagnosed age was 5.70 months.Conclusion The initial screening rate,initial screening pass rate,re-screening rate,re-checking recall rate,and diagnosis rate of Ningbo City have met the requirements of the guidelines and are at a leading level in China.The next step is to upgrade the information network to improve the diagnosis rate at 3 months of age,the intervention rate at 6 months of age,and the follow-up management of children with hearing loss are the key points in the future work of neonatal hearing screening.

Objective:To analyze the treatment-free remission (TFR) outcomes after discontinuation of tyrosine kinase inhibitor (TKI) in children with chronic myeloid leukemia (CML).Methods:In this retrospective cohort study, clinical data of 14 chronic phase CML children aged <18 years who had achieved stable deep molecular response (DMR) for ≥ 2 years after standardized treatment with TKI and had a strong desire to discontinue TKI at Henan Cancer Hospital from September 30, 2016 to January 30, 2022 were collected retrospectively. According to the different TFR outcomes after discontinuation of TKI, patients were divided into loss of major molecular response (MMR) group and without loss of MMR group, differences in clinical characteristics between the two groups of children were analyzed using Mann-Whitney U test and Fisher exact test. Results:Out of 14 children with TKI discontinuation, 7 were male and 7 were female. The age at diagnosis was 14.0 (4.8, 17.0) years, and the age at TKI discontinuation was 22.0 (12.5, 27.0) years. Among them, 8 children were treated with imatinib prior to TKI discontinuation and 6 children were treated with second-line substitution of the second-generation TKI nilotinib or dasatinib prior to TKI discontinuation. The follow-up time was 37.0 (27.8, 47.5) months, and 7 cases lost MMR at the time of discontinuation of 3.0 (2.0, 11.0) months. Eight children gained TFR at 6 months, 7 children gained TFR at 12 and 24 months. Amongst the 6 children who received second-generation TKI prior to TKI discontinuation, 2 children lost MMR at 3 and 11 months and 4 children gained TFR, among the 8 children who discontinued imatinib, 5 children lost MMR at the time 3.0 (2.0, 9.0) months and 3 children gained TFR. The age at diagnosis and TKI discontinuation, the time from TKI treatment to the acquisition of DMR, the duration of TKI treatment before TKI discontinuation, the duration of DMR before TKI discontinuation, and the number of children treated with second-generation TKI were not statistically different between the 7 children in the group that did not lose the MMR and the 7 children in the group that lost the MMR (all P>0.05) . All the 7 children with confirmed loss of MMR immediately restarted TKI therapy, and all regained DMR after 2.0 (2.0, 11.0) months of therapy. None of the children had disease progression. After TKI discontinued, only 1 child had mild bone pain, which could be relieved by oral antipyretic analgesic drugs. Conclusions:Children with CML who have achieved a durable stable DMR for≥2 years on TKI therapy can discontinue the TKI and obtain TFR. Both the longer duration of TKI therapy, the longer duration of DMR and the use of second-generation TKI therapy before TKI discontinuation, may allow more children with CML who are expecting TKI discontinuation to have access to TFR.

OBJECTIVE To observe the expression of micro ribonucleic acid-146a(miR-146a)in peripheral blood of the children with hand-foot-mouth disease(HFMD)caused by enterovirus 71(EV71)infection and analyze the clinical significance.METHODS A total of 45 children with HFMD induced by non-EV71 infection who were trea-ted in Hangzhou Children's Hospital from Jul.2023 to Jan.2024 were assigned as the HFMD group,meanwhile,15 healthy children who received physical examination were chosen as the healthy group.The baseline clinical data were compared between the two groups.The expression level of miR-146a in peripheral blood mononuclear cells(PBMCs)was detected by real-time polymerase chain reaction(RT-PCR),the levels of blood routine indexes and relevant biochemical indexes were detected.The association of expression of peripheral blood miR-146a,routine indexes with the HFMD induced by non-EV71 infection was observed.The value of miR-146a in diagnosis of HFMD induced by non-EV71 infection was analyzed by means of receiver operating characteristic(ROC)curves.RESULTS The expression level of miR-146a in PBMCs was 0.78(0.69,1.08)in the HFMD group,1.43(1.11,1.62)in the healthy group,and there was significant difference(Z=-3.927,P＜0.001);there were significant difference values in WBC and CRP between the two groups(t=5.188,P＜0.001;Z=-4.986,P＜0.001).Among the children in the HFMD group,the expression level of miR-146a was 0.83(0.70,1.27)in the children with common HFMD,0.73(0.66,0.79)in the children with severe HFMD,and there was significant difference(Z=-2.130,P=0.032).ROC curve analysis showed that the area under the curve(AUC)of the miR-146a was 0.841 in prediction of HFMD caused by non-EV71 infection.CONCLUSIONS The children with HFMD caused by non-EV71 infection show the remarkable decline of miR-146a in PMMCs.The low expression level of miR-146a may be the predictive factor for risk of HFMD caused by non-EV71 infection and severe HFMD,it has certain predictive value and can be used as blood marker for the children with HFMD.