This paper summarizes the clinical experience in treating children adenoid hypertrophy using the "opening the orifices and regulating qi method". It is considered that the pathogenesis of adenoid hypertrophy in children is rooted in dysfunction of zangfu （脏腑） organs， with binding of phlegm and stasis as the branch. Obstruction of the cervical passes and rebellious， chaotic qi flow run through the entire course of the disease. The "opening the orifices and regulating qi method" is proposed， which emphasizes the regulation of the lung， spleen， liver， and stomach. By opening the cervical passes， regulating zangfu organs， and eliminating phlegm and stasis to harmonize the ascent and descent of qi， a comprehensive application of external traditional Chinese medicine （TCM） therapies， such as acupuncture， umbilical moxibustion with medicinals， collateral bloodletting， and sole therapy， is utilized. Addressing both root and branch causes， this approach provides new perspectives for treating children adenoid hypertrophy using external TCM therapies.

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.

To enhance the trustworthiness,security,and convenience of research data management and pro-mote the deep utilization of clinical research data,it introduces core technologies such as data sandboxing,ze-ro-trust architecture,elastic resource scheduling in cloud computing,and data lakes to construct a clinical research trusted data space with trusted management,resource interaction,and value co-creation capabilities.This trusted data space provides a secure and efficient platform for data processing and analysis through strict network access control,dynamic authentication,data anonymization,and digital watermarking technologies.It ensures the secure flow and precise traceability of research data throughout its lifecycle,effectively facilitating resource interaction and value co-creation.The implementation offers a valuable technical reference and practical guidance for other hospitals aiming to build trusted research data platforms.

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.

ObjectiveTo develop a patient-reported traditional Chinese medicine kidney deficiency pattern (TCM-KDP) scale for colorectal cancer (CRC) patients and evaluate its reliability and validity.MethodsWe administered the TCM-KDP questionnaire to postoperative patients with stage II and III CRC as part of a multicenter randomized controlled trial (RCT) conducted in China from December 2018 to September 2021. The TCM-KDP scale consists of eight items on patient-reported symptoms and is scored on a five-point Likert scale. The scale’s reliability was assessed using Cronbach’s α and test-retest reliability, while content validity was evaluated with the content validity index. We compared the differences in serum cytokine levels and other clinical factors between patients with higher and lower KDP scores.ResultsOf the 378 patients analyzed in the original RCT, 352 (93.2%) completed the TCM-KDP questionnaire. The Cronbach’s α of the eight-item TCM-KDP scale was 0.734, and the test-retest reliability was 0.745. Our exploratory factor analysis yielded eight factors that explained the variance of 50.34%. The mean TCM-KDP score was 2.80 ± 0.92. Compared with patients with stage II CRC, those with stage III CRC had significantly higher TCM-KDP scores (2.25 vs. 2.50, P = .026). We categorized all patients into high- or low-KDP score groups (the cut-off score was 2.8). Patients with lower TCM-KDP scores had significantly higher serum interleukin-1β expression levels (P = .04).ConclusionThe patient-reported TCM-KDP scale demonstrated relatively good feasibility, internal consistency, and test-retest reliability among patients with CRC. Future studies could apply this scale to other cancer types and diseases.

OBJECTIVE To compare the ability of ultra-high-resolution CT(U-HRCT)and multi-slice spiral CT(MSCT)to display key vocal transmission structures in the middle ear.METHODS Subjects with normal middle ear structures who underwent 0.1 mm layer thickness U-HRCT and 0.625 mm layer thickness MSCT scans at the same time in Beijing Friendship Hospital affiliated to Capital Medical University from December 2019 to August 2024 were retrospectively enrolled.Two experienced head and neck radiologists reconstruct standard transsectional,coronal images based on the thinnest layer thickness.According to the 5-point method,16 key sound transmission structures of the middle ear,including malleus,incus and stapes,as well as joints,ligaments and tendons,were evaluated for image quality scoring.The standard deviation(SD)value,signal noise ratio(SNR),and contrast noise ratio(CNR)of bone in the malleus region and intratympanic gas were measured and calculated on the two examination images.RESULTS Thirty patients(47 sides)with normal middle ear structure were included,including 18 males and 12 females.The two physicians compared the results of U-HRCT in showing malleus head,malleus neck,malleus handle,incus body,long process,and short process,5 points accounted for 100%,and the 5-point scores of incudomalleolar joint space,incudostapedial joint space,stapes footplate and annular ligament were 100%,98.29%,75.83%and 77.83%,respectively,which were significantly higher than those of MSCT(P<0.001).In addition,U-HRCT showed higher scores for lenticular process,stapes head,anterior arch of stapes,posterior arch of stapes,annular ligament,stapes muscle,and tendo musculi tensoris tympani than MSCT(P<0.001),and the lenticular process showed a 100%display rate.There was no significant difference in the SNR between the two groups(P>0.05),but the SD value of the malleus in U-HRCT was 161.6±36.4,which was significantly lower than that in MSCT(297.8±128.1),and the difference was statistically significant(P<0.001).CONCLUSION U-HRCT can clearly visualize the key sound transmission structures of the middle ear,and its visualization ability is significantly better than that of MSCT.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

BACKGROUND:Facet joint osteoarthritis is acknowledged as a significant contributor to lower back pain in the geriatric population.The advent of an innovative spinal facet joint fusion device presents a therapeutic option for intervening during the initial stages of facet joint osteoarthritis,and significantly reduces the incidence of a series of complications caused by poor early conservative treatment and late surgical treatment.However,its effect on the biomechanics of the lumbar spine is unknown.OBJECTIVE:To investigate the biomechanical disparities between the novel lumbar zygapophyseal joint fusion device and traditional fusion devices.METHODS:A comprehensive three-dimensional finite element model of the L3-S1 lumbar spine was established and validated.Based on this intact model,three groups of surgical models were constructed:a bilateral pedicle screw fixation model,a bilateral novel facet joint fusion fixation model,and a bilateral facet screw fixation model,with the surgical segment designated as L4-5.Under a load of 500 N,a torque of 7.5 Nm was applied to all lumbar models to calculate the range of motion,displacement values,and intervertebral disc stress values at the L4-5 segment;stress values at the L3-4 and L5-S1 segments were also measured.RESULTS AND CONCLUSION:(1)Compared with the intact model,the range of motion at the L4-5 segment was reduced in all surgical models.(2)The novel device exhibited the smallest range of motion at the L4-5 segment under left and right rotational conditions;the greatest range of motion at the L4-5 segment under extension conditions;and a greater range of motion under other conditions than the bilateral pedicle screw fixation model.(3)The novel device demonstrated the smallest displacement values at the L4-5 segment under left and right rotational conditions;under other conditions,the displacement values at the L4-5 segment were greater than those in the bilateral pedicle screw fixation model.(4)In terms of stress distribution at the L4-5 segment,the novel device consistently exhibited the smallest values across all conditions.(5)For the L3-4 segment,the novel device showed the greatest stress values under extension and left and right rotational conditions,while under other conditions,the values were lower than those in the bilateral pedicle screw fixation model.(6)Compared with pedicle screw fixation,the novel device produced smaller stress values at the L5-S1 segment.(7)This study indicates that,compared with pedicle screw fixation,the novel device impacts the biomechanics of the lumbar spine by fusing the facet joints.It provides stability while preserving the range of motion at the surgical segment and reduces stress on the intervertebral discs of the surgical and adjacent segments,thereby potentially delaying disc degeneration.This suggests that the novel device can achieve biomechanical effects similar to those of pedicle screw fixation in theory.