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.

Objective To analyze the screening results of prostate cancer(PCa)based on the serum prostate-specific antigen(PSA)level in middle-aged and elderly men in Kaifeng,so as to provide reference for optimizing the early screening strategy of PCa.Methods A multicenter cross-sectional design was adopted to analyze the serum PSA test results of male residents aged 52 to 94 collected from 14 community health service stations in Kaifeng during Jul.2024 and Apr.2025. Participants with PSA ≥4 μg/L were recommended to undergo prostate biopsy at a tertiary grade A hospital for a confirmed diagnosis.Multivariate logistic regression was used to analyze the influencing factors of referral compliance.The PSA positivity rate,referral loss rate,puncture willingness rate,and biopsy positivity rate were calculated.Results A total of 2812 men received free PSA screening.Among them,248 had abnormal PSA(≥4 μg/L),with a positive rate of 8.8%(248/2812).Only 105 cases were successfully referred to a tertiary grade A hospital,with a referral rate of 42.3%(105/248),and the referral loss rate reached 57.7%.Fifty-seven patients were advised to undergo prostate biopsy,but only 23 actually underwent prostate biopsy,and the willingness rate was 40.4%(23/57).Fourteen cases were diagnosed with PCa and the positive rate of prostate biopsy was 60.9%(14/23).The overall detection rate of PCa was 0.5%(14/2812).In the screening stage,the median PSA was 6.7(4.8-11.2)μg/L.The Spearman correlation analysis showed a positive correlation between participant age and PSA level(r_s=0.28,P＜0.001).In the diagnostic stage,only 40.4% of the referred patients underwent prostate biopsy,and the loss rate reached 59.6%.The median PSA in the PCa group was significantly higher than that in the non-PCa group(9.8 μg/L vs. 5.1 μg/L,P=0.002).Multivariate logistic regression analyses showed that advanced age(OR=1.08)and educational level of primary school or below(OR=3.32)were independent influencing factors for referral disorders(P＜0.001).In terms of screening efficacy,the overall biopsy positivity rate was 5.6%(14/248).Conclusion Conducting PCa screening based on PSA testing among middle-aged and elderly male residents can significantly increase the detection rate of clinically meaningful PCa,thereby improving the overall prognosis of patients.However,insufficient referral compliance(only 42.3%)and low puncture willingness rate(only 40.4%)have limited the screening benefits.Therefore,the research suggests that measures such as strengthening health education,popularizing relevant knowledge,and providing referral support are needed to reduce the churn rate.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

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 investigate the mechanism by which AGE receptor(RAGE)antagonist FPS-ZM1 inhibits AGE accumulation and promotes wound repair in rats with diabetic foot ulcer(DFU).Methods A total of 30 SD rats were divided into normal control(Con)group,sham operation group(Sham),DFU group,FPS-ZM1 treatment group(DFU+FPS-ZM1),and phosphate buffer saline treatment group(DFU+PBS),with 6 rats in each group.Masson staining was used to evaluate the wound surface structure.ELISA was used to detect the expression of AGE,TNF-α,matrix metalloproteinase 9(MMP-9),and VEGF proteins in serum and tissues,and Western blot method was used to test the expression of RAGE,VEGF receptor(VEGFR),CD31,and nuclear factor κB(NF-κB)proteins.Results Compared with the Con and Sham groups,the collagen fibers had less indigo staining,disordered arrangement and sparse distribution in DFU group.Compared with the DFU and DFU+PBS groups,the DFU+FPS-ZM1 group showed obvious blue staining of collagen fibers in the wound granulation tissue,and the number of deposition layers was relatively neat and orderly.Compared with Sham group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues were increased(P<0.05),and the expressions of VEGF protein and CD31 and VEGFR proteins in serum and tissues were decreased in DFU group(P<0.05).Compared with DFU group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues decreased(P<0.05),and the expression of VEGF protein and CD31 and VEGFR proteins in serum and tissues increased in DFU+FPS-ZM1 group(P<0.05).Compared with DFU+FPS-ZM1 group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues increased(P<0.05),and the expressions of VEGF protein,CD31 and VEGFR proteins in serum tissues decreased in DFU+PBS group(P<0.05).Conclusions The RAGE antagonist FPS-ZM1 down-regulates MMP-9 and up-regulates VEGF by inhibiting the NF-κB inflammatory signaling pathway,and promotes DFU wound healing.

Objective:To observe the current status of the use of personal protective equipment (PPE) by the dust working population, and to analyze the factors affecting its use, so as to provide a reference basis for proposing scientific intervention methods.Methods:From October to December 2023, random sampling method was used to conduct a self-designed Questionnaire on the Use of Personal Protective Equipment by the Dust Working Population. A total of 1216 dust workers were randomly selected from each city in Guangdong Province, and their mask wearing status was evaluated. The Wilcoxon rank sum test was used for comparison between measurement data sets, and the Chi-square test or Fisher exact probability method was used for counting data. A binary logistic regression model was used to analyze the factors affecting the use of PPE in dust workers.Results:The correct rate of wearing PPE in dust working group was 66.12% (804/1216). In univariate analysis, there were statistical significances in different knowledge score, wearing PPE to reduce exposure to dust particles, wearing occupational health protective equipment such as masks was uncomfortable, wearing occupational health protective equipment such as masks reduced work efficiency, attending pre-employment occupational health examination, attending occupational health examination on a regular basis, receiving occupational health training during work in the enterprise, being urged or reminded by workmates, supervisors, or family members to use PPE, the correct use of PPE when workers or shift leaders were exposed to dust particles, second-hand smoke inhalation, smoking, and alcohol consumption ( P<0.05). Multiple logistic regression results showed that gender ( OR=2.00, 95% CI: 1.48-2.72), knowledge score ( OR=1.18, 95% CI: 1.11-1.26), neutral attitude towards the discomfort of wearing occupational health protective equipment such as masks during work ( OR=1.64, 95% CI: 1.18-2.27), and participation in pre-job occupational health examination ( OR=0.23, 95% CI: 0.10-0.54) were the main influencing factors on the use of PPE to be worn correctly ( P<0.05) . Conclusion:The rate of correct wearing of PPE for dust working population still needs to be improved. Factors such as gender, knowledge score, neutral attitude towards the discomfort of wearing masks during work, and participation in pre-job occupational health examination may be the influencing factors on the use of PPE for dust working population.