Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

The Solomon four-group design， a critical method for improving internal validity in clinical research， can reduce bias and control the interference of Hawthorne effects and pretest sensitization on research results， which offers unique advantages in evaluating complex intervention outcomes. This paper systematically outlined the core framework and key points of statistical analysis of the Solomon four-group design， summarized its applications in clinical research at home and abroad， explored its advantages and limitations， and discussed the potential value in traditional Chinese medicine （TCM） clinical trials. It is believed that the Solomon four-group design can help distinguish between testing effects and intervention effects in TCM clinical studies， and reduce the bias in the evaluation of subjective indicators. Meanwhile， given the complexity of the Solomon four-group design and the particularity of TCM clinical research， it is proposed that future TCM clinical studies should focus on using psychological scales， know-ledge， attitude， and behavior measurements， and other similat evaluations as endpoints. It also advocates strengthening interdisciplinary collaboration to provide new methodological paths for TCM clinical research.

Contralateral radiculopathy, a postoperative complication after transforaminal lumbar interbody fusion, refers to postoperative numbness, pain and other neurological symptoms of the lower limb on the side opposite to the symptomatic or the surgical decompression side. Its main causes include excessive restoration of lordosis, intervertebral space tilt caused by improper cage position, poor screw position, new protrusion of nucleus pulposus or bone graft, and hematoma. At present, attention to this complication is gradually increasing. This review summarizes its risk factors from the recent related reports of the condition and puts forward preventive measures in order to promote the preventive awareness of this complication.

Objective To explore the distribution of common TCM syndromes and symptoms of insomnia;To prepare for the construction of the theoretical framework and item pool of syndrome diagnosis and efficacy evaluation scale.Methods TCM guideline standards of insomnia,textbooks and journals over the years were retrieved,the information of TCM syndromes,syndrome elements and symptoms was extracted,the guideline textbook and journal database were established,and descriptive statistics,association rules,systematic clustering,factor analysis,potential categories and implicit structure analysis were carried out.Results Totally 116 guide standards and textbooks over the years were included,and 454 articles of journals were included.The high-frequency symptoms accounted for≥3%of the guide textbooks and journal databases were 87 and 79 categories,respectively,and the cumulative proportion was 87.48%and 87.75%,respectively.According to the analysis results,five common TCM syndromes and their characteristic symptom classification of insomnia were finally deduced.According to the frequency/person time distribution,they were heart and spleen deficiency syndrome,yin deficiency and fire hyperactivity syndrome,liver fire disturbing heart syndrome,phlegm heat disturbing heart syndrome,heart and gallbladder qi deficiency syndrome.Conclusion There are five common TCM syndromes of insomnia,and the characteristic symptoms of each TCM syndrome provide a reference source for the theoretical framework of syndrome diagnosis and efficacy evaluation scale and the establishment of item pool.

Inflammatory bowel disease (IBD) is a chronic immune-mediated gastrointestinal inflammatory disorder that includes ulcerative colitis (UC) and Crohn disease (CD). Currently, there is a lack of reliable diagnostic methods for IBD. Endoscopic biopsy is one of the common methods for detecting IBD, but it has limitations. In non-invasive assessment of IBD, ultrasound, CT, and MRI are less invasive and better tolerated than endoscopy, and can show the complete bowel condition, assess the thickness of the intestinal wall, and detect parenteral complications. Meanwhile, with the further study of IBD biomarkers, SPECT and PET are increasingly used in early diagnosis and efficacy monitoring of IBD, especially in patients who cannot tolerate invasive tests. The continuous developments of the above imaging techniques provide a more minimally invasive method than endoscopy for early non-invasive diagnosis and efficacy monitoring of IBD. This article reviews the latest research and application progress of the above imaging techniques in IBD.

Objective:To explore any effect of excitatory and inhibitory multi-focal transcranial direct current stimulation (m-tDCS) on cortical functioning in healthy adults.Methods:Fifteen healthy participants received 20-minute excitatory and inhibitory episodes of m-tDCS targeting C1-C2-FC1-FC2. Finite element analysis and functional near-infrared spectroscopy were then used to model the normal component of the electric field (En) applied and to monitor the oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (THb) concentrations in the targeted regions during the stimulation.Results:The excitatory protocol induced En values of 0.057V/m and 0.058V/m in the left and right hemispheres, respectively, with an average of 0.058V/m, while the inhibitory one evoked corresponding En values of -0.057V/m and -0.058V/m with an average of -0.058V/m. During excitatory m-tDCS, HbO and THb concentrations in the target cortices were higher than in the inhibitory protocol, with significant differences at FC1, FC2, and C2 for HbO, and at FC2 and C2 for THb. However, no significant inter-group differences in HbR concentrations were observed. Moreover, either protocol induced severe adverse reactions including pain, though the pain decreased with prolonged stimulation.Conclusions:Both excitatory and inhibitory m-tDCS modulate cortical function among healthy individuals. Excitatory m-tDCS is the more effective in enhancing cortical excitability.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To develop and validate the reliability and validity of the care giver assessment via observation (CGAO) in general hospital .Methods:From July 4, 2022 to June 24, 2023, a total of 120 adult inpatients with somatic diseases in Peking Union Medical College Hospital were selected by cluster sampling. All patients completed the CGAO, union physio-psycho-social assessment questionnaire (UPPSAQ-70) and patient health questionnaire-9 item (PHQ-9) assessment simultaneously. Exploratory factor analysis and item response theory analysis were used to explore the structural validity of CGAO by SPSS 26.0 software.The symptoms items and suicide risk assessed by UPPSAQ-70 and PHQ-9 were used as criteria to verify criterion validity.Results:Through exploratory factor analysis, a single-factor model could be constructed. The analysis based on item response theory suggested that it had a good fit with the single-factor stepwise response model ( χ2/ df=1.307, RMSEA=0.051, CFI=0.986, TLI=0.983). The CGAO total score was significantly positively correlated with the total scores of PHQ-9 and UPPSAQ-70 ( r=0.639, 0.518, both P<0.001). The Cronbach's α coefficient of the CGAO full scale was 0.735. Conclusion:CGAO has good reliability and validity in evaluating mental behavior of patients, and is suitable for early recognition of mental behavior abnormalities of inpatients in general hospitals.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

This artical starts from the perspective of"earth stagnation and wood depression"to analyze the dynamic mutual impairment process between breast cancer and mixed anxiety and depressive disorder(MADD),integrating pathological evidence of mutual causality between physical impairment and internal injury by emotional distress,to provide a theoretical framework elucidating the intrinsic unity of the microbiota-neuro-tumor interaction network in the comorbidity vicious cycle.The comorbidity of breast cancer and MADD manifests dynamic mutually aggravating impairment,with core pathogenesis according to the traditional Chinese medicine theory of"earth stagnation and wood depression":spleen earth stagnation leads to dampness-turbidity obstruction,while dysfunction of the middle jiao pivot result in abnormal liver qi conveyance and dispersion;liver depression transforming into fire further over-restricts on spleen earth.Mutual over-restriction and counter-restriction between the two causes toxic fire,phlegm and blood stasis to conglomerate into masses.The lingering disease progression causes mutual damage between body and spirit,leading to progressive consumption until physical collapse and spiritual decline,ultimately culminating in earth exhaustion and wood withering,toxins infiltrating the extraordinary vessels,and divorce of yin-yang.Gut microbiota dysbiosis induces abnormalities in the metabolic-immune-neuroendocrine network,driving emotional disorders and interacting with the tumor microenvironment to exacerbate deterioration.This mechanism not only validates the concept of"earth stagnation and wood depression-mutual physical-mental impairment",but also elucidates its role in inducing multi-system cascade failure,ultimately culminating in a pathological process marked by the emergence of severe clinical manifestations.