OBJECTIVE To investigate the mechanism of isochlorogenic acid A against hepatocellular carcinoma based on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and multi-omics technology. METHODS The invasion rate and migration rate of human hepatocellular carcinoma HepG2 cells after 48 h of intervention with 0 （control group）， 0.25 and 0.5 mg/mL isochlorogenic acid A were examined； mRNA expression of DEP domain-containing mTOR-interacting protein （DEPTOR）， the protein expressions of mTOR， PI3K and phosphatase and tensin homologue deleted on chromosome ten （PTEN）， as well as the phosphorylation level of Akt protein were determined in the cells. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry， and differential metabolites were screened and subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis； transcriptomics monitoring was conducted by RNA sequencing， and differentially expressed genes were screened and subjected to gene ontology （GO） and KEGG pathway enrichment analyses. RESULTS Compared with the control group， intervention with 0.25 and 0.5 mg/mL isochlorogenic acid A for 48 h significantly inhibited the invasion rate and migration rate of HepG2 cells， significantly up-regulated the mRNA expression of DEPTOR and the protein expression of PTEN， and significantly down-regulated the protein expression of PI3K and the phosphorylation level of Akt protein （except for 0.25 mg/mL isochlorogenic acid A） （ P ＜0.05）. A total of 304 differential metabolites and 212 differentially expressed genes were screened by multi-omics analysis. KEGG pathway enrichment analysis suggested that isochlorogenic acid A regulated key signaling of HepG2 cell growth mainly by inhibiting the PI3K/Akt signaling pathway， synergizing with metabolic reprogramming such as mTOR signaling pathway， ferroptosis， pentose phosphate pathway and purine/pyrimidine metabo lism. CONCLUSIONS The anti-hepatocellular carcinoma effect of isochlorogenic acid A is associated with the blockade of abnormal activation of the PI3K/Akt/mTOR signaling pathway. In addition， it may also be related to the inhibition of the pentose phosphate pathway and purine/pyrimidine metabolism， as well as the induction of ferroptosis，etc.

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Objective:To explore the potential profile characteristics and influencing factors of rehabilitation motivation in elderly patients with first stroke, so as to provide reference for promoting precise rehabilitation mode.Methods:A convenience sampling method was employed to conduct a cross-sectional survey of elderly patients with first stroke admitted to the Huanhu Hospital Affiliated to Tianjin Medical University from October 2024 to March 2025. The survey utilized a general information questionnaire, the Motivation in Stroke Patients for Rehabilitation Scale, the Perceived Social Support Scale (PSSS), the Exercise Adherence Questionnaire (EAQ), and the Stroke Stigma Scale (SSS). Potential categories of rehabilitation motivation among elderly patients with first stroke were identified using latent profile analysis, and the influencing factors of these potential categories were explored using the ordered multinomial Logistic regression.Results:A total of 290 survey questionnaires were distributed, and 281 valid questionnaires were collected, with an effective response rate of 96.9%(281/290). Among 281 elderly patients with first stroke, there were 152 males and 129 females, with an age of (68.68 ± 6.89) years. The score of the Motivation in Stroke Patients for Rehabilitation Scale was 56.00 (36.00, 68.00) points. Rehabilitation motivation among elderly patients with first stroke could be categorized into three groups: low motivation-lack of family support and unclear goals group (44.1%, 124/281), moderate motivation-social reintegration driven but insufficient behavior group (41.3%, 116/281), and high motivation autonomous planning adaptation and value internalization group (14.6%, 41/281). The ordered multinomial Logistic regression analysis showed that compared to patients aged ≥80 years, patients aged 60-69 years were less likely to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=0.231, P<0.05). Compared to patients with a per capita monthly income of ≥5 001 yuan, patients with a per capita monthly income of 3 001-5 000 yuan were more likely to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=2.340, P<0.05). Compared to heavily dependent patients, patients who were completely independent ( OR=0.160, P<0.05), mildly dependent ( OR=0.155, P<0.01), and moderately dependent ( OR=0.211, P<0.05) were less likely to belong to the high motivation autonomous planning adaptation and value internalization group. The higher the EAQ score, the more likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=1.139, P<0.01). The higher the PSSS score, the more likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=1.108, P<0.01). The higher the SSS score, the less likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=0.787, P<0.01). Conclusions:Healthcare professionals can develop targeted intervention strategies based on the characteristics and influencing factors of patients' different rehabilitation motivations, thereby enhancing their rehabilitation motivation and promoting patient recovery.

Objective:To explore the potential categories of internal ability of elderly patients with ischemic stroke, identify the influencing factors and propose corresponding nursing interventions.Methods:This was a cross-sectional study. From January 2025 to May 2025, the elderly patients with ischemic stroke in Tianjin Huanhu Hospital were selected by convenient sampling method. The general information questionnaire, the Internal Capacity Assessment Scale for the Older People, the Health Literacy Scale for stroke patients and the Perceived Social Support Scale were used to investigate. To determine latent categories of patients' intrinsic capacity, potential profile analysis was employed. Subsequently, multivariable Logistic regression examined factors associated with these categories.Results:A total of 260 survey questionnaires were distributed, and 256 valid questionnaires were finally collected, with an effective response rate of 98.46% (256/260). Among of them, there were 166 males and 90 females, aged 68.00 (63.00, 74.00) years.The intrinsic ability of elderly patients with ischemic stroke could be divided into three potential categories: low sensation-low exercise group (27.0%, 69/256), relatively stable intrinsic ability group (37.5%, 96/256) and low cognition-low psychology group (35.5%, 91/256). Multivariable Logistic regression showed that advanced age (compared to the low sensation-low exercise group, OR=0.902; compared to the relatively stable intrinsic ability group, OR=0.813), smoking (compared to the low sensation-low exercise group, OR=0.459; compared to the relatively stable intrinsic ability group, OR=0.442), the lower the Barthel index (compared to the low sensation-low exercise group, ≤40 points with OR=0.157; 41-60 points with OR=0.285) were more likely to enter the low cognition-low psychology group (all P<0.05); other chronic disease types ≤1 (compared to the low cognition-low psychology group, OR=2.630), higher health literacy scores (compared to the low cognition-low psychology group, OR=1.033) were more likely to enter the relatively stable intrinsic ability group (both P<0.05); and stroke frequency was the first occurrence (compared to the low cognition-low psychology group, OR=2.725) was more likely to enter the low sensation-low exercise group ( P<0.05). Conclusions:In older adults with ischemic stroke, the characteristics of intrinsic ability are clearly categorized. To enhance patient outcomes, healthcare professionals are advised to tailor nursing interventions based on the unique features and specific influencing factors associated with each potential category.

The early diagnosis of prostate cancer(PCa)heavily relies on advances of biopsy techniques.Traditional transrectal ultrasound(TRUS)-guided biopsy is associated with high infection risks and significant miss rates.Transperineal prostate biopsy,with the advantage of spatial sampling,can reduce infection and has the potential for image fusion.With the development of image-guided technology,multimodal image fusion technology has achieved a paradigm shift from"probabilistic sampling"to"precise localization"through the visualization of lesion structure and function.Among them,ultrasound-guided techniques,including transrectal real-time elastography(TRTE),transrectal contrast-enhanced ultrasound(TRCEUS),micro-ultrasound(Micro-US),and multiparametric ultrasound(mpUS),have significantly improved the accuracy of prostate biopsy.MRI-guided techniques,including multiparametric magnetic resonance imaging(mpMRI),MRI-fusion targeted biopsy(MRI-fusion-TB),and the integration of MRI-guided targeted biopsy and systematic biopsy can enhance the specificity of detection and reduce the misdiagnosis rate of clinically significant prostate cancer(csPCa).PET-guided technology can integrate metabolic function information of lesions with high-resolution structural features,demonstrating significant advantages in PCa diagnosis.AI-assisted technology also shows great potential in prostate targeted biopsy.Future research should focus on the integration of targeted biopsy with emerging imaging technologies or AI tools to improve the early diagnosis rate of PCa and optimize clinical decision-making.

Objective:To document any effect of repeated high-frequency repetitive transcranial magnetic stimulation (rTMS) using double-cone coils on the lower limb motor function of stroke survivors.Methods:A total of 40 stroke survivors were randomly divided into an rTMS group and a sham stimulation group, each of 20. The rTMS group received rTMS at 10Hz with a double-cone coil, while a coil that produced sound but no magnetic stimulation was used with the sham group. The treatments were administered daily, five times a week, for three weeks. Before as well as after 1, 2 and 3 weeks of treatment, lower limb motor function, balance, and the root mean square (RMS) and median frequency (MF) of the rectus femoris and tibialis anterior muscles were evaluated using the Fugl-Meyer lower extremity assessment (FMA-LE), the Berg Balance Scale (BBS), the Modified Barthel Index (MBI), Brunnstrom staging, the TecnoBody balance assessment system, and surface electromyography.Results:Compared with the sham stimulation group, the BBS score of the rTMS group was significantly higher after 2 weeks of treatment, and both the FMA-LE and BBS scores were significantly higher after 3 weeks. The average Brunnstrom stage in the sham group had increased significantly after 3 weeks, but in the rTMS group it had increased after 2 weeks. By 3 weeks there were no significant differences between the two groups. In terms of movement control, the average motion ellipse area in the rTMS group was significantly smaller than among the sham group after 2 weeks, and after 3 weeks the average motion trajectory length was significantly shorter than in the sham group. The average RMS of the rectus femoris in the rTMS group was significantly higher than the sham group′s average after 3 weeks of treatment, indicating improved muscle activation.Conclusions:High-frequency rTMS using a conical coil can effectively improve the lower limb motor function and balance ability of stroke survivors, demonstrating promising clinical application potential.

The early diagnosis of prostate cancer(PCa)heavily relies on advances of biopsy techniques.Traditional transrectal ultrasound(TRUS)-guided biopsy is associated with high infection risks and significant miss rates.Transperineal prostate biopsy,with the advantage of spatial sampling,can reduce infection and has the potential for image fusion.With the development of image-guided technology,multimodal image fusion technology has achieved a paradigm shift from"probabilistic sampling"to"precise localization"through the visualization of lesion structure and function.Among them,ultrasound-guided techniques,including transrectal real-time elastography(TRTE),transrectal contrast-enhanced ultrasound(TRCEUS),micro-ultrasound(Micro-US),and multiparametric ultrasound(mpUS),have significantly improved the accuracy of prostate biopsy.MRI-guided techniques,including multiparametric magnetic resonance imaging(mpMRI),MRI-fusion targeted biopsy(MRI-fusion-TB),and the integration of MRI-guided targeted biopsy and systematic biopsy can enhance the specificity of detection and reduce the misdiagnosis rate of clinically significant prostate cancer(csPCa).PET-guided technology can integrate metabolic function information of lesions with high-resolution structural features,demonstrating significant advantages in PCa diagnosis.AI-assisted technology also shows great potential in prostate targeted biopsy.Future research should focus on the integration of targeted biopsy with emerging imaging technologies or AI tools to improve the early diagnosis rate of PCa and optimize clinical decision-making.

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2-3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced in-testinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12-/-mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

OBJECTIVE: To assess the feasibility of first polar body transfer (PB1T) combined with preimplantation mitochondrial genetic testing for blocking the transmission of a pathogenic mitochondrial DNA 8993T>G mutation. METHODS: A Chinese family affected with Leigh syndrome which had attended the Reproductive Medicine Centre of the First Affiliated Hospital of Anhui Medical University in September 2021 was selected as the study subject. Controlled ovarian hyperstimulation was carried out for the proband after completing the detection of the mitochondrial DNA 8993T>G mutation load among the pedigree members. Mature MII oocytes were inseminated by intracytoplasmic sperm injection (ICSI), cultured in vitro for 5 to 6 days to the blastocyst stage, and trophoblastocytes were obtained by microbiopsy. Mitochondrial DNA testing (PGT-MT) and chromosomal aneuploidy (PGT-A) analyses were carried out after whole-genome amplification, and the embryos with zero mutation load were selected for transfer. Amniotic fluid and umbilical cord blood samples were collected during middle pregnancy and after birth respectively for mitochondrial DNA testing to verify the reliability of embryo screening. As an attempt, PB1 with good morphology of MII oocytes was selected for transfer into the enucleated oocytoplasm from healthy donors, followed by ICSI fertilization, blastocyst culture and PGT of embryos using the same procedure. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (No. 2021zhyx-B12). RESULTS: An antagonist protocol was used for ovarian stimulation, and a total of 19 oocytes were obtained, of which 14 MII were fertilized by ICSI, and 2 had developed into blastocysts. PGT-MT was carried out on biopsied trophoblastocytes, in which the mitochondrial DNA 8993T>G mutation load was not detected in one embryo, the other was 100% mutated, and the mutation loads of the remaining unfertilized eggs and developmentally arrested embryos ranged from 0% ~ 100%, presenting a clear biased distribution. With fully informed consent, one PGT-MT zero mutation load blastocyst was transferred and clinical pregnancy was achieved. Mitochondrial DNA and chromosomal testing of amniotic fluid cells during middle pregnancy had revealed no abnormalities. The proband had delivered a healthy boy through Caesarean section at 39⁺⁵ weeks of gestation, and no mutation was detected in the cord blood sample. Five well-formed PBs from 14 eggs were selected for PB1 transfer, followed by ICSI and culture, and two of the reconstituted embryos had formed blastocysts, with none of the above mutations detected in the biopsied samples. CONCLUSION The PGT-MT technology can help families affected with mitochondrial diseases to have healthy offspring. PB1 transfer in combination with ICSI and PGT-MT holds the promise of turning waste into treasure and providing an alternative means of fertility for such families.
Humans ; Preimplantation Diagnosis/methods* ; Female ; DNA, Mitochondrial/genetics* ; Genetic Testing/methods* ; Pregnancy ; Mitochondrial Diseases/genetics* ; Polar Bodies ; Adult ; Feasibility Studies ; Sperm Injections, Intracytoplasmic/methods* ; Embryo Transfer/methods* ; Mutation ; Male ; Blastocyst/metabolism* ; Pedigree

Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.